Rameshbabu, S., Labadie, B. W., Argulian, A. & Patnaik, A. Targeting innate immunity in cancer therapy. Vaccines 9, 138 (2021).
Saeed, A. et al. Regulation of cGAS-mediated immune responses and immunotherapy. Adv. Sci. 7, 1902599 (2020).
Kumar, V. Toll-like receptors in sepsis-associated cytokine storm and their endogenous negative regulators as future immunomodulatory targets. Int. Immunopharmacol. 89, 107087 (2020).
Merien, F. A journey with Elie Metchnikoff: from innate cell mechanisms in infectious diseases to quantum biology. Front. Public Health 4, 125 (2016).
Chen, Z. et al. Role of oxidative stress in the pathogenesis of nonalcoholic fatty liver disease. Free Radic. Biol. Med. 152, 116–141 (2020).
Zhao, T. et al. Reactive oxygen species-based nanomaterials for the treatment of myocardial ischemia reperfusion injuries. Bioact. Mater. 7, 47–72 (2022).
Pidwill, G. R. et al. The role of macrophages in Staphylococcus aureus infection. Front. Immunol. 11, 620339 (2020).
Yang, L. & Zhang, Y. Tumor-associated macrophages: from basic research to clinical application. J. Hematol. Oncol. 10, 58 (2017).
Kim, J. H. et al. Immunomodulatory functional foods and their molecular mechanisms. Exp. Mol. Med. 54, 1–11 (2022).
Hu, W. & Spaink, H. P. The role of TLR2 in infectious diseases caused by mycobacteria: from cell biology to therapeutic target. Biology 11, 246 (2022).
Ruiz-Baca, E. et al. The role of macrophages in the host’s defense against Sporothrix schenckii. Pathogens 10, 905 (2021).
Feraoun, Y. et al. The route of vaccine administration determines whether blood neutrophils undergo long-term phenotypic modifications. Front. Immunol. 12, 784813 (2021).
Jia, Y. & Wei, Y. Modulators of MicroRNA function in the immune system. Int. J. Mol. Sci. 21, 2357 (2020).
Li, Y. et al. Functional and therapeutic significance of tumor-associated macrophages in colorectal cancer. Front. Oncol. 12, 781233 (2022).
Padron, J. G., Saito Reis, C. A. & Kendal-Wright, C. E. The role of danger associated molecular patterns in human fetal membrane weakening. Front. Physiol. 11, 602 (2020).
Keewan, E. & Naser, S. A. The role of notch signaling in macrophages during inflammation and infection: implication in rheumatoid arthritis?. Cells 9, 111 (2020).
Zhang, Y. H., He, M., Wang, Y. & Liao, A. H. Modulators of the balance between M1 and M2 macrophages during pregnancy. Front. Immunol. 8, 120 (2017).
Bleul, T. et al. Different innate immune responses in BALB/c and C57BL/6 strains following corneal transplantation. J. Innate Immun. 13, 49–59 (2021).
Abdelaziz, M. H. et al. Alternatively activated macrophages; a double-edged sword in allergic asthma. J. Transl. Med. 18, 58 (2020).
Suuring, M. & Moreau, A. Regulatory macrophages and tolerogenic dendritic cells in myeloid regulatory cell-based therapies. Int. J. Mol. Sci. 22, 7970 (2021).
Han, S. et al. Differential responsiveness of monocyte and macrophage subsets to interferon. Arthritis Rheumatol. 72, 100–113 (2020).
Li, Y., Yun, K. & Mu, R. A review on the biology and properties of adipose tissue macrophages involved in adipose tissue physiological and pathophysiological processes. Lipids Health Dis. 19, 164 (2020).
Cai, Y. et al. Single-cell transcriptomics of blood reveals a natural killer cell subset depletion in tuberculosis. EBioMedicine 53, 102686 (2020).
Lv, B. et al. Biomaterial-supported MSC transplantation enhances cell-cell communication for spinal cord injury. Stem Cell Res. Ther. 12, 36 (2021).
Schymik, H. S., Dahlem, C., Barghash, A. & Kiemer, A. K. Comment on: The m6A Reader IGF2BP2 Regulates Macrophage Phenotypic Activation and Inflammatory Diseases by Stabilizing TSC1 and PPARγ. Adv. Sci. 9, e2104372 (2022).
Shaheryar, Z. A. et al. Neuroinflammatory triangle presenting novel pharmacological targets for ischemic brain injury. Front. Immunol. 12, 748663 (2021).
Boutilier, A. J. & Elsawa, S. F. Macrophage polarization states in the tumor microenvironment. Int. J. Mol. Sci. 22, 6995 (2021).
Xia, P. et al. Research progress on Toll-like receptor signal transduction and its roles in antimicrobial immune responses. Appl. Microbiol. Biotechnol. 105, 5341–5355 (2021).
Javaid, N. & Choi, S. Toll-like receptors from the perspective of cancer treatment. Cancers 12, 297 (2020).
Callahan, V. et al. The pro-inflammatory chemokines CXCL9, CXCL10 and CXCL11 are upregulated following SARS-CoV-2 infection in an AKT-dependent manner. Viruses 13, 1062 (2021).
Kashfi, K., Kannikal, J. & Nath, N. Macrophage reprogramming and cancer therapeutics: role of iNOS-derived NO. Cells 10, 3194 (2021).
Filipek, A., Mikolajczyk, T. P., Guzik, T. J. & Naruszewicz, M. Oleacein and foam cell formation in human monocyte-derived macrophages: a potential strategy against early and advanced atherosclerotic lesions. Pharmaceuticals 13, 64 (2020).
Meduri, G. U. & Chrousos, G. P. General adaptation in critical illness: glucocorticoid receptor-alpha master regulator of homeostatic corrections. Front. Endocrinol. 11, 161 (2020).
Summers, K. M., Bush, S. J. & Hume, D. A. Network analysis of transcriptomic diversity amongst resident tissue macrophages and dendritic cells in the mouse mononuclear phagocyte system. PLoS Biol. 18, e3000859 (2020).
Chang, W. T. et al. Mutant glucocorticoid receptor binding elements on the interleukin-6 promoter regulate dexamethasone effects. BMC Immunol. 22, 24 (2021).
De Cunto, G. et al. Alveolar macrophage phenotype and compartmentalization drive different pulmonary changes in mouse strains exposed to cigarette smoke. Copd 17, 429–443 (2020).
Cardoso, F. O. et al. Modulation of cytokines and extracellular matrix proteins expression by Leishmania amazonensis in susceptible and resistant mice. Front. Microbiol. 11, 1986 (2020).
Gabr, M. M. et al. Interaction of opioids with TLR4-mechanisms and ramifications. Cancers 13, 5274 (2021).
Choi, Y. S. et al. Immunomodulatory scaffolds derived from lymph node extracellular matrices. ACS Appl. Mater. Interfaces 13, 14037–14049 (2021).
Cai, C. W. et al. Th17 cells provide mucosal protection against gastric Trypanosoma cruzi infection. Infect. Immun. 89, e0073820 (2021).
Palmieri, E. M. et al. Nitric oxide orchestrates metabolic rewiring in M1 macrophages by targeting aconitase 2 and pyruvate dehydrogenase. Nat. Commun. 11, 698 (2020).
Han, I. H., Song, H. O. & Ryu, J. S. IL-6 produced by prostate epithelial cells stimulated with Trichomonas vaginalis promotes proliferation of prostate cancer cells by inducing M2 polarization of THP-1-derived macrophages. PLoS Negl. Trop. Dis. 14, e0008126 (2020).
Huang, J. et al. Promising therapeutic targets for treatment of rheumatoid arthritis. Front. Immunol. 12, 686155 (2021).
Mata, R. et al. The dynamic inflammatory tissue microenvironment: signality and disease therapy by biomaterials. Research 2021, 4189516 (2021).
Medrano-Bosch, M., Moreno-Lanceta, A. & Melgar-Lesmes, P. Nanoparticles to target and treat macrophages: the Ockham’s concept?. Pharmaceutics 13, 1340 (2021).
Liu, Y. et al. Metabolic reprogramming in macrophage responses. Biomark. Res. 9, 1 (2021).
Ricketts, T. D., Prieto-Dominguez, N., Gowda, P. S. & Ubil, E. Mechanisms of macrophage plasticity in the tumor environment: manipulating activation state to improve outcomes. Front. Immunol. 12, 642285 (2021).
Salminen, A. Increased immunosuppression impairs tissue homeostasis with aging and age-related diseases. J. Mol. Med. 99, 1–20 (2021).
Ordikhani, F. et al. Macrophages in organ transplantation. Front. Immunol. 11, 582939 (2020).
Poh, A. R. & Ernst, M. Tumor-associated macrophages in pancreatic ductal adenocarcinoma: therapeutic opportunities and clinical challenges. Cancers 13, 2860 (2021).
Zhao, H. et al. Inflammation and tumor progression: signaling pathways and targeted intervention. Signal Transduct. Target Ther. 6, 263 (2021).
Yin, Y. et al. Colorectal cancer-derived small extracellular vesicles promote tumor immune evasion by upregulating PD-L1 expression in tumor-associated macrophages. Adv. Sci. 9, 2102620 (2022).
Müller, A. K. et al. Mouse modeling dissecting macrophage-breast cancer communication uncovered roles of PYK2 in macrophage recruitment and breast tumorigenesis. Adv. Sci. 9, e2105696 (2022).
Gurvich, O. L. et al. Transcriptomics uncovers substantial variability associated with alterations in manufacturing processes of macrophage cell therapy products. Sci. Rep. 10, 14049 (2020).
Ahuja, S. & Lazar, I. M. Systems-level proteomics evaluation of microglia response to tumor-supportive anti-inflammatory cytokines. Front. Immunol. 12, 646043 (2021).
Ye, J. et al. Promoting musculoskeletal system soft tissue regeneration by biomaterial-mediated modulation of macrophage polarization. Bioact. Mater. 6, 4096–4109 (2021).
Keegan, A. D., Leonard, W. J. & Zhu, J. Recent advances in understanding the role of IL-4 signaling. Fac. Rev. 10, 71 (2021).
Medvedeva, G. F. et al. How macrophages become transcriptionally dysregulated: a hidden impact of antitumor therapy. Int. J. Mol. Sci. 22, 2662 (2021).
Duan, Z. & Luo, Y. Targeting macrophages in cancer immunotherapy. Signal Transduct. Target Ther. 6, 127 (2021).
Jurga, A. M., Paleczna, M. & Kuter, K. Z. Overview of general and discriminating markers of differential microglia phenotypes. Front. Cell. Neurosci. 14, 198 (2020).
Grzywa, T. M. et al. Myeloid cell-derived arginase in cancer immune response. Front. Immunol. 11, 938 (2020).
Labani-Motlagh, A., Ashja-Mahdavi, M. & Loskog, A. The tumor microenvironment: a milieu hindering and obstructing antitumor immune responses. Front. Immunol. 11, 940 (2020).
Wang, R. et al. Selective uptake of carboxylated multi-walled carbon nanotubes by class A type 1 scavenger receptors and impaired phagocytosis in alveolar macrophages. Nanomaterials 10, 2417 (2020).
Adlerz, K. M., Aranda-Espinoza, H. & Hayenga, H. N. Substrate elasticity regulates the behavior of human monocyte-derived macrophages. Eur. Biophys. J. 45, 301–309 (2016).
Scheraga, R. G. et al. TRPV4 mechanosensitive ion channel regulates lipopolysaccharide-stimulated macrophage phagocytosis. J. Immunol. 196, 428–436 (2016).
Kortesoja, M., Trofin, R. E. & Hanski, L. A platform for studying the transfer of Chlamydia pneumoniae infection between respiratory epithelium and phagocytes. J. Microbiol. Methods 171, 105857 (2020).
Baranov, M. V. et al. Modulation of immune responses by particle size and shape. Front. Immunol. 11, 607945 (2020).
Martin, K. E. & García, A. J. Macrophage phenotypes in tissue repair and the foreign body response: implications for biomaterial-based regenerative medicine strategies. Acta Biomater. 133, 4–16 (2021).
Polidoro, R. B., Hagan, R. S., de Santis Santiago, R. & Schmidt, N. W. Overview: systemic inflammatory response derived from lung injury caused by SARS-CoV-2 infection explains severe outcomes in COVID-19. Front. Immunol. 11, 1626 (2020).
Sehlmeyer, K., Ruwisch, J., Roldan, N. & Lopez-Rodriguez, E. Alveolar dynamics and beyond – the importance of surfactant protein C and cholesterol in lung homeostasis and fibrosis. Front. Physiol. 11, 386 (2020).
Ogger, P. P. & Byrne, A. J. Macrophage metabolic reprogramming during chronic lung disease. Mucosal Immunol. 14, 282–295 (2021).
Matheson, L. A., Maksym, G. N., Santerre, J. P. & Labow, R. S. Cyclic biaxial strain affects U937 macrophage-like morphology and enzymatic activities. J. Biomed. Mater. Res. A 76, 52–62 (2006).
Lee, H. G. et al. Aggravation of inflammatory response by costimulation with titanium particles and mechanical perturbations in osteoblast- and macrophage-like cells. Am. J. Physiol. Cell Physiol. 304, C431–C439 (2013).
Oya, K., Sakamoto, N. & Sato, M. Hypoxia suppresses stretch-induced elongation and orientation of macrophages. Biomed. Mater. Eng. 23, 463–471 (2013).
Li, C. et al. Tumor-associated macrophages: potential therapeutic strategies and future prospects in cancer. J. Immunother. Cancer. 9, e001341 (2021).
Wu, W. et al. The autophagy-initiating kinase ULK1 controls RIPK1-mediated cell death. Cell Rep. 31, 107547 (2020).
Zhu, S. et al. Roles of tumor-associated macrophages in tumor progression: implications on therapeutic strategies. Exp. Hematol. Oncol. 10, 60 (2021).
Schultze, J. L. & Schmidt, S. V. Molecular features of macrophage activation. Semin. Immunol. 27, 416–423 (2015).
Bonilla, D. L. et al. Autophagy regulates phagocytosis by modulating the expression of scavenger receptors. Immunity 39, 537–547 (2013).
Pu, Q. et al. Atg7 deficiency intensifies inflammasome activation and pyroptosis in Pseudomonas Sepsis. J. Immunol. 198, 3205–3213 (2017).
Malaguarnera, L. Vitamin D3 as potential treatment adjuncts for COVID-19. Nutrients 12, 3512 (2020).
Maphasa, R. E., Meyer, M. & Dube, A. The macrophage response to mycobacterium tuberculosis and opportunities for autophagy inducing nanomedicines for tuberculosis therapy. Front. Cell. Infect. Microbiol. 10, 618414 (2020).
Leseigneur, C., Lê-Bury, P., Pizarro-Cerdá, J. & Dussurget, O. Emerging evasion mechanisms of macrophage defenses by pathogenic bacteria. Front. Cell. Infect. Microbiol. 10, 577559 (2020).
Kelava, I. et al. Atg5-deficient mice infected with Francisella tularensis LVS demonstrate increased survival and less severe pathology in internal organs. Microorganisms 8, 1531 (2020).
Wu, S. et al. Salmonella interacts with autophagy to offense or defense. Front. Microbiol. 11, 721 (2020).
Biasizzo, M. & Kopitar-Jerala, N. Interplay between NLRP3 inflammasome and autophagy. Front. Immunol. 11, 591803 (2020).
Kundu, M. & Basu, J. The role of microRNAs and long non-coding RNAs in the regulation of the immune response to Mycobacterium tuberculosis infection. Front. Immunol. 12, 687962 (2021).
Seim, G. L. et al. Two-stage metabolic remodelling in macrophages in response to lipopolysaccharide and interferon-γ stimulation. Nat. Metab. 1, 731–742 (2019).
Ramalho, R. et al. Immunometabolism: new insights and lessons from antigen-directed cellular immune responses. Semin. Immunopathol. 42, 279–313 (2020).
Luque-Campos, N. et al. The macrophage response is driven by mesenchymal stem cell-mediated metabolic reprogramming. Front. Immunol. 12, 624746 (2021).
Martínez-Reyes, I. & Chandel, N. S. Mitochondrial TCA cycle metabolites control physiology and disease. Nat. Commun. 11, 102 (2020).
Palmieri, E. M., McGinity, C., Wink, D. A. & McVicar, D. W. Nitric oxide in macrophage immunometabolism: hiding in plain sight. Metabolites 10, 429 (2020).
Pålsson-McDermott, E. M. & O’Neill, L. A. J. Targeting immunometabolism as an anti-inflammatory strategy. Cell Res. 30, 300–314 (2020).
Tabas, I. & Bornfeldt, K. E. Intracellular and intercellular aspects of macrophage immunometabolism in atherosclerosis. Circ. Res. 126, 1209–1227 (2020).
Lacroix, M. et al. Metabolic functions of the tumor suppressor p53: implications in normal physiology, metabolic disorders, and cancer. Mol. Metab. 33, 2–22 (2020).
Mehla, K. & Singh, P. K. Metabolic regulation of macrophage polarization in cancer. Trends Cancer 5, 822–834 (2019).
Behmoaras, J. The versatile biochemistry of iron in macrophage effector functions. Febs J. 288, 6972–6989 (2021).
Santarsiero, A. et al. Phenolic compounds of red wine Aglianico del Vulture modulate the functional activity of macrophages via inhibition of NF-κB and the citrate pathway. Oxid. Med. Cell. Longev. 2021, 5533793 (2021).
Loras, A., Segovia, C. & Ruiz-Cerdá, J. L. Epigenomic and metabolomic integration reveals dynamic metabolic regulation in bladder cancer. Cancers 13, 2719 (2021).
Xiao, H. et al. M2-like tumor-associated macrophage-targeted codelivery of STAT6 inhibitor and IKKβ siRNA induces M2-to-M1 repolarization for cancer immunotherapy with low immune side effects. ACS Cent. Sci. 6, 1208–1222 (2020).
Läsche, M., Emons, G. & Gründker, C. Shedding new light on cancer metabolism: a metabolic tightrope between life and death. Front. Oncol. 10, 409 (2020).
Daemen, S. & Schilling, J. D. The interplay between tissue niche and macrophage cellular metabolism in obesity. Front. Immunol. 10, 3133 (2019).
Li, Q. & Xiang, M. Metabolic reprograming of MDSCs within tumor microenvironment and targeting for cancer immunotherapy. Acta Pharmacol. Sin. 43, 1337–1348 (2022).
Chang, Y. H., Weng, C. L. & Lin, K. I. O-GlcNAcylation and its role in the immune system. J. Biomed. Sci. 27, 57 (2020).
Bosch, M. et al. Mammalian lipid droplets are innate immune hubs integrating cell metabolism and host defense. Science 370, eaay8085 (2020).
Fortuny, L. & Sebastián, C. Sirtuins as metabolic regulators of immune cells phenotype and function. Genes 12, 1698 (2021).
Lee, K. M. C., Achuthan, A. A. & Hamilton, J. A. GM-CSF: a promising target in inflammation and autoimmunity. Immunotargets Ther. 9, 225–240 (2020).
Wilkinson, H. et al. PAR-1 signaling on macrophages is required for effective in vivo delayed-type hypersensitivity responses. iScience 24, 101981 (2021).
Zajd, C. M. et al. Bone marrow-derived and elicited peritoneal macrophages are not created equal: the questions asked dictate the cell type used. Front. Immunol. 11, 269 (2020).
Karagiannidis, I. et al. G-CSF and G-CSFR induce a pro-tumorigenic macrophage phenotype to promote colon and pancreas tumor growth. Cancers 12, 2868 (2020).
Giacomantonio, M. A. et al. Quantitative proteome responses to oncolytic reovirus in GM-CSF- and M-CSF-differentiated bone marrow-derived cells. J. Proteome Res. 19, 708–718 (2020).
Ataya, A. et al. The role of GM-CSF autoantibodies in infection and autoimmune pulmonary alveolar proteinosis: a concise review. Front. Immunol. 12, 752856 (2021).
Gu, T. et al. Cytokine signature induced by SARS-CoV-2 spike protein in a mouse model. Front. Immunol. 11, 621441 (2020).
Yang, S., Liu, Q. & Liao, Q. Tumor-associated macrophages in pancreatic ductal adenocarcinoma: origin, polarization, function, and reprogramming. Front. Cell Dev. Biol. 8, 607209 (2020).
Ivashkiv, L. B. IFNγ: signalling, epigenetics and roles in immunity, metabolism, disease and cancer immunotherapy. Nat. Rev. Immunol. 18, 545–558 (2018).
Jha, A. K. et al. Network integration of parallel metabolic and transcriptional data reveals metabolic modules that regulate macrophage polarization. Immunity 42, 419–430 (2015).
Mouton, A. J., Li, X., Hall, M. E. & Hall, J. E. Obesity, hypertension, and cardiac dysfunction: novel roles of immunometabolism in macrophage activation and inflammation. Circ. Res. 126, 789–806 (2020).
Corcoran, S. E. & O’Neill, L. A. HIF1α and metabolic reprogramming in inflammation. J. Clin. Invest. 126, 3699–3707 (2016).
Qualls, J. E. et al. Sustained generation of nitric oxide and control of mycobacterial infection requires argininosuccinate synthase 1. Cell Host Microbe 12, 313–323 (2012).
Mao, Y., Shi, D., Li, G. & Jiang, P. Citrulline depletion by ASS1 is required for proinflammatory macrophage activation and immune responses. Mol. Cell 82, 527–541.e527 (2022).
Ji, L. et al. Slc6a8-mediated creatine uptake and accumulation reprogram macrophage polarization via regulating cytokine responses. Immunity 51, 272–284.e277 (2019).
Riesberg, L. A. et al. Creatinine downregulates TNF-α in macrophage and T cell lines. Cytokine 110, 29–38 (2018).
Wang, S. et al. Metabolic reprogramming of macrophages during infections and cancer. Cancer Lett. 452, 14–22 (2019).
Russell, D. G., Huang, L. & VanderVen, B. C. Immunometabolism at the interface between macrophages and pathogens. Nat. Rev. Immunol. 19, 291–304 (2019).
Tan, Z. et al. Pyruvate dehydrogenase kinase 1 participates in macrophage polarization via regulating glucose metabolism. J. Immunol. 194, 6082–6089 (2015).
Li, X. et al. β‑glucan, a dectin‑1 ligand, promotes macrophage M1 polarization via NF‑κB/autophagy pathway. Int. J. Oncol. 54, 271–282 (2019).
Braverman, J. & Stanley, S. A. Nitric oxide modulates macrophage responses to Mycobacterium tuberculosis infection through activation of HIF-1α and repression of NF-κB. J. Immunol. 199, 1805–1816 (2017).
Hollenbaugh, J. A. et al. Metabolic profiling during HIV-1 and HIV-2 infection of primary human monocyte-derived macrophages. Virology 491, 106–114 (2016).
O’Neill, L. A., Kishton, R. J. & Rathmell, J. A guide to immunometabolism for immunologists. Nat. Rev. Immunol. 16, 553–565 (2016).
Eming, S. A., Murray, P. J. & Pearce, E. J. Metabolic orchestration of the wound healing response. Cell Metab. 33, 1726–1743 (2021).
Leone, R. D. & Powell, J. D. Metabolism of immune cells in cancer. Nat. Rev. Cancer 20, 516–531 (2020).
Chen, S. et al. Tumor-associated macrophages are shaped by intratumoral high potassium via Kir2.1. Cell Metab. 34, 1843–1859.e1811 (2022).
Liu, C. et al. Treg cells promote the SREBP1-dependent metabolic fitness of tumor-promoting macrophages via repression of CD8(+) T cell-derived interferon-γ. Immunity 51, 381–397.e386 (2019).
Zhang, M. et al. Pancreatic cancer cells render tumor-associated macrophages metabolically reprogrammed by a GARP and DNA methylation-mediated mechanism. Signal Transduct. Target Ther. 6, 366 (2021).
Klein, K. et al. Role of mitochondria in cancer immune evasion and potential therapeutic approaches. Front. Immunol. 11, 573326 (2020).
Walsh, M. C., Lee, J. & Choi, Y. Tumor necrosis factor receptor- associated factor 6 (TRAF6) regulation of development, function, and homeostasis of the immune system. Immunol. Rev. 266, 72–92 (2015).
Ross, E. A., Devitt, A. & Johnson, J. R. Macrophages: the good, the bad, and the gluttony. Front. Immunol. 12, 708186 (2021).
Han, X., Ding, S., Jiang, H. & Liu, G. Roles of macrophages in the development and treatment of gut inflammation. Front. Cell. Dev. Biol. 9, 625423 (2021).
Haubruck, P. et al. Monocytes, macrophages, and their potential niches in synovial joints – therapeutic targets in post-traumatic osteoarthritis? Front. Immunol. 12, 763702 (2021).
Li, J. et al. Tailoring materials for modulation of macrophage fate. Adv. Mater. 33, e2004172 (2021).
Meli, V. S. et al. Biophysical regulation of macrophages in health and disease. J. Leukoc. Biol. 106, 283–299 (2019).
Vania, V. et al. The interplay of signaling pathway in endothelial cells-matrix stiffness dependency with targeted-therapeutic drugs. Biochim. Biophys. Acta Mol. Basis. Dis. 1866, 165645 (2020).
Vorselen, D. et al. Phagocytic ‘teeth’ and myosin-II ‘jaw’ power target constriction during phagocytosis. Elife 10, e68627 (2021).
Deng, R. et al. Periosteal CD68(+) F4/80(+) macrophages are mechanosensitive for cortical bone formation by secretion and activation of TGF-β1. Adv. Sci. 9, e2103343 (2022).
Jäger, A. V. et al. The inflammatory response induced by Pseudomonas aeruginosa in macrophages enhances apoptotic cell removal. Sci. Rep. 11, 2393 (2021).
Tedesco, S. et al. Convenience versus biological significance: are PMA-differentiated THP-1 cells a reliable substitute for blood-derived macrophages when studying in vitro polarization? Front. Pharmacol. 9, 71 (2018).
Tan, K. S. et al. The role of titanium surface topography on J774A.1 macrophage inflammatory cytokines and nitric oxide production. Biomaterials 27, 5170–5177 (2006).
Negrescu, A. M. & Cimpean, A. The state of the art and prospects for osteoimmunomodulatory biomaterials. Materials 14, 1357 (2021).
Sun, S. J. et al. Effects of TiO2 nanotube layers on RAW 264.7 macrophage behaviour and bone morphogenetic protein-2 expression. Cell Prolif. 46, 685–694 (2013).
Hotchkiss, K. M. et al. Titanium surface characteristics, including topography and wettability, alter macrophage activation. Acta Biomater. 31, 425–434 (2016).
Anderson, J. A., Lamichhane, S. & Mani, G. Macrophage responses to 316 L stainless steel and cobalt chromium alloys with different surface topographies. J. Biomed. Mater. Res. A 104, 2658–2672 (2016).
Wang, T. et al. Topographical modulation of macrophage phenotype by shrink-film multi-scale wrinkles. Biomater. Sci. 4, 948–952 (2016).
Bartneck, M. et al. Inducing healing-like human primary macrophage phenotypes by 3D hydrogel coated nanofibres. Biomaterials 33, 4136–4146 (2012).
Zaveri, T. D. et al. Integrin-directed modulation of macrophage responses to biomaterials. Biomaterials 35, 3504–3515 (2014).
Castro-Núñez, L. et al. Shear stress is required for the endocytic uptake of the factor VIII-von Willebrand factor complex by macrophages. J. Thromb. Haemost. 10, 1929–1937 (2012).
Seneviratne, A. N. et al. Low shear stress induces M1 macrophage polarization in murine thin-cap atherosclerotic plaques. J. Mol. Cell. Cardiol. 89, 168–172 (2015).
Atcha, H. et al. Mechanically activated ion channel Piezo1 modulates macrophage polarization and stiffness sensing. Nat. Commun. 12, 3256 (2021).
He, Y. et al. Myeloid Piezo1 deletion protects renal fibrosis by restraining macrophage infiltration and activation. Hypertension 79, 918–931 (2022).
Zhang, X. et al. Piezo1-mediated mechanosensation in bone marrow macrophages promotes vascular niche regeneration after irradiation injury. Theranostics 12, 1621–1638 (2022).
Geng, J. et al. TLR4 signalling via Piezo1 engages and enhances the macrophage mediated host response during bacterial infection. Nat. Commun. 12, 3519 (2021).
Ma, S. et al. A role of PIEZO1 in iron metabolism in mice and humans. Cell 184, 969–982.e913 (2021).
Wang, M., Xia, F., Wei, Y. & Wei, X. Molecular mechanisms and clinical management of cancer bone metastasis. Bone Res. 8, 30 (2020).
Monteith, A. J. et al. Neutrophil extracellular traps enhance macrophage killing of bacterial pathogens. Sci. Adv. 7, eabj2101 (2021).
Vorobjeva, N. V. & Chernyak, B. V. NETosis: molecular mechanisms, Role in physiology and pathology. Biochemistry 85, 1178–1190 (2020).
López-Jiménez, A. T. & Mostowy, S. Emerging technologies and infection models in cellular microbiology. Nat. Commun. 12, 6764 (2021).
Brinkmann, V. et al. Neutrophil extracellular traps kill bacteria. Science 303, 1532–1535 (2004).
Hu, J. et al. Targeting neutrophil extracellular traps in severe acute pancreatitis treatment. Ther. Adv. Gastroenterol. 13, 1756284820974913 (2020).
Yousefi, S. et al. Catapult-like release of mitochondrial DNA by eosinophils contributes to antibacterial defense. Nat. Med. 14, 949–953 (2008).
Wong, K. W. & Jacobs, W. R. Jr. Mycobacterium tuberculosis exploits human interferon γ to stimulate macrophage extracellular trap formation and necrosis. J. Infect. Dis. 208, 109–119 (2013).
Aulik, N. A., Hellenbrand, K. M. & Czuprynski, C. J. Mannheimia haemolytica and its leukotoxin cause macrophage extracellular trap formation by bovine macrophages. Infect. Immun. 80, 1923–1933 (2012).
Liu, P. et al. Escherichia coli and Candida albicans induced macrophage extracellular trap-like structures with limited microbicidal activity. PLoS ONE 9, e90042 (2014).
Bonne-Année, S. et al. Extracellular traps are associated with human and mouse neutrophil and macrophage mediated killing of larval Strongyloides stercoralis. Microbes Infect. 16, 502–511 (2014).
Linnenberger, R. et al. Statins and Bempedoic acid: different actions of cholesterol inhibitors on macrophage activation. Int. J. Mol. Sci. 22, 12480 (2021).
Doster, R. S., Rogers, L. M., Gaddy, J. A. & Aronoff, D. M. Macrophage extracellular traps: a scoping review. J. Innate Immun. 10, 3–13 (2018).
Hu, G. et al. High-throughput phenotypic screen and transcriptional analysis identify new compounds and targets for macrophage reprogramming. Nat. Commun. 12, 773 (2021).
Yousefi, S. et al. In vivo evidence for extracellular DNA trap formation. Cell Death Dis. 11, 300 (2020).
Fukuchi, M. et al. How to detect eosinophil ETosis (EETosis) and extracellular traps. Allergol. Int. 70, 19–29 (2021).
Zhang, Y., Rayner, B. S., Jensen, M. & Hawkins, C. L. In vitro stimulation and visualization of extracellular trap release in differentiated human monocyte-derived macrophages. J. Vis. Exp. https://doi.org/10.3791/60541 (2019).
Schorn, C. et al. Monosodium urate crystals induce extracellular DNA traps in neutrophils, eosinophils, and basophils but not in mononuclear cells. Front. Immunol. 3, 277 (2012).
Chow, O. A. et al. Statins enhance formation of phagocyte extracellular traps. Cell Host Microbe 8, 445–454 (2010).
Halder, L. D. et al. Factor H binds to extracellular DNA traps released from human blood monocytes in response to Candida albicans. Front. Immunol. 7, 671 (2016).
Chen, X. et al. Macrophage polarization and its role in the pathogenesis of acute lung injury/acute respiratory distress syndrome. Inflamm. Res. 69, 883–895 (2020).
Tugal, D., Liao, X. & Jain, M. K. Transcriptional control of macrophage polarization. Arterioscler. Thromb. Vasc. Biol. 33, 1135–1144 (2013).
Lawrence, T. & Natoli, G. Transcriptional regulation of macrophage polarization: enabling diversity with identity. Nat. Rev. Immunol. 11, 750–761 (2011).
Biswas, S. K. & Mantovani, A. Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat. Immunol. 11, 889–896 (2010).
Fu, X. L. et al. Interleukin 6 induces M2 macrophage differentiation by STAT3 activation that correlates with gastric cancer progression. Cancer Immunol. Immunother. 66, 1597–1608 (2017).
Sica, A. & Mantovani, A. Macrophage plasticity and polarization: in vivo veritas. J. Clin. Invest. 122, 787–795 (2012).
Szanto, A. et al. STAT6 transcription factor is a facilitator of the nuclear receptor PPARγ-regulated gene expression in macrophages and dendritic cells. Immunity 33, 699–712 (2010).
Kamerkar, S. et al. Exosome-mediated genetic reprogramming of tumor-associated macrophages by exoASO-STAT6 leads to potent monotherapy antitumor activity. Sci. Adv. 8, eabj7002 (2022).
Fujioka, S. et al. NF-kappaB and AP-1 connection: mechanism of NF-kappaB-dependent regulation of AP-1 activity. Mol. Cell. Biol. 24, 7806–7819 (2004).
Porta, C. et al. Tolerance and M2 (alternative) macrophage polarization are related processes orchestrated by p50 nuclear factor kappaB. Proc. Natl Acad. Sci. USA 106, 14978–14983 (2009).
Zhang, G. & Ghosh, S. Toll-like receptor-mediated NF-kappaB activation: a phylogenetically conserved paradigm in innate immunity. J. Clin. Invest. 107, 13–19 (2001).
Ziegler-Heitbrock, L. The p50-homodimer mechanism in tolerance to LPS. J. Endotoxin Res. 7, 219–222 (2001).
Honda, K. & Taniguchi, T. Toll-like receptor signaling and IRF transcription factors. IUBMB Life. 58, 290–295 (2006).
Takaoka, A., Tamura, T. & Taniguchi, T. Interferon regulatory factor family of transcription factors and regulation of oncogenesis. Cancer Sci. 99, 467–478 (2008).
Wang, N., Liang, H. & Zen, K. Molecular mechanisms that influence the macrophage m1-m2 polarization balance. Front. Immunol. 5, 614 (2014).
Chuffa, L. G. et al. Melatonin attenuates the TLR4-mediated inflammatory response through MyD88- and TRIF-dependent signaling pathways in an in vivo model of ovarian cancer. BMC Cancer 15, 34 (2015).
Zhao, W. et al. LY294002 inhibits TLR3/4-mediated IFN-β production via inhibition of IRF3 activation with a PI3K-independent mechanism. FEBS Lett. 586, 705–710 (2012).
Hu, X., Chakravarty, S. D. & Ivashkiv, L. B. Regulation of interferon and Toll-like receptor signaling during macrophage activation by opposing feedforward and feedback inhibition mechanisms. Immunol. Rev. 226, 41–56 (2008).
Krausgruber, T. et al. IRF5 promotes inflammatory macrophage polarization and TH1-TH17 responses. Nat. Immunol. 12, 231–238 (2011).
Negishi, H. et al. Negative regulation of Toll-like-receptor signaling by IRF-4. Proc. Natl Acad. Sci. USA 102, 15989–15994 (2005).
Satoh, T. et al. The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection. Nat. Immunol. 11, 936–944 (2010).
Grygiel-Górniak, B. Peroxisome proliferator-activated receptors and their ligands: nutritional and clinical implications–a review. Nutr. J. 13, 17 (2014).
Montaigne, D., Butruille, L. & Staels, B. PPAR control of metabolism and cardiovascular functions. Nat. Rev. Cardiol. 18, 809–823 (2021).
Devchand, P. R. et al. The PPARalpha-leukotriene B4 pathway to inflammation control. Nature 384, 39–43 (1996).
Rigamonti, E., Chinetti-Gbaguidi, G. & Staels, B. Regulation of macrophage functions by PPAR-alpha, PPAR-gamma, and LXRs in mice and men. Arterioscler. Thromb. Vasc. Biol. 28, 1050–1059 (2008).
Penas, F. et al. Treatment in vitro with PPARα and PPARγ ligands drives M1-to-M2 polarization of macrophages from T. cruzi-infected mice. Biochim. Biophys. Acta 1852, 893–904 (2015).
Li, J., Guo, C. & Wu, J. 15-Deoxy-∆-(12,14)-prostaglandin J2 (15d-PGJ2), an endogenous ligand of PPAR-γ: function and mechanism. PPAR Res. 2019, 7242030 (2019).
Ricote, M. et al. The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation. Nature 391, 79–82 (1998).
Martinez, F. O., Helming, L. & Gordon, S. Alternative activation of macrophages: an immunologic functional perspective. Annu. Rev. Immunol. 27, 451–483 (2009).
Odegaard, J. I. et al. Alternative M2 activation of Kupffer cells by PPARdelta ameliorates obesity-induced insulin resistance. Cell Metab. 7, 496–507 (2008).
Zhu, K. Y. et al. The functions and prognostic value of Krüppel-like factors in breast cancer. Cancer Cell Int. 22, 23 (2022).
Liao, X. et al. Krüppel-like factor 4 regulates macrophage polarization. J. Clin. Invest. 121, 2736–2749 (2011).
Knights, A. J. et al. Krüppel-like factor 3 (KLF3) suppresses NF-κB-driven inflammation in mice. J. Biol. Chem. 295, 6080–6091 (2020).
Goodman, W. A. et al. KLF6 contributes to myeloid cell plasticity in the pathogenesis of intestinal inflammation. Mucosal Immunol. 9, 1250–1262 (2016).
Date, D. et al. Kruppel-like transcription factor 6 regulates inflammatory macrophage polarization. J. Biol. Chem. 289, 10318–10329 (2014).
Yuan, Y. et al. The transcription factor KLF14 regulates macrophage glycolysis and immune function by inhibiting HK2 in sepsis. Cell. Mol. Immunol. 19, 504–515 (2022).
Wu, Q. et al. Hypoxia-inducible factors: master regulators of hypoxic tumor immune escape. J. Hematol. Oncol. 15, 77 (2022).
Takeda, N. et al. Differential activation and antagonistic function of HIF-{alpha} isoforms in macrophages are essential for NO homeostasis. Genes Dev. 24, 491–501 (2010).
Deng, Y. et al. The role and regulation of Maf proteins in cancer. Biomark. Res. 11, 17 (2023).
Liu, M. et al. Transcription factor c-Maf is a checkpoint that programs macrophages in lung cancer. J. Clin. Invest. 130, 2081–2096 (2020).
Filiberti, S. et al. Self-renewal of macrophages: tumor-released factors and signaling pathways. Biomedicines 10, 2709 (2022).
Chen, S., Yang, J., Wei, Y. & Wei, X. Epigenetic regulation of macrophages: from homeostasis maintenance to host defense. Cell. Mol. Immunol. 17, 36–49 (2020).
Yin, Y. et al. Impact of cytosine methylation on DNA binding specificities of human transcription factors. Science 356, (2017).
Schübeler, D. Function and information content of DNA methylation. Nature 517, 321–326 (2015).
Cheng, C. et al. SOCS1 hypermethylation mediated by DNMT1 is associated with lipopolysaccharide-induced inflammatory cytokines in macrophages. Toxicol. Lett. 225, 488–497 (2014).
Yan, J. et al. Diabetes impairs wound healing by Dnmt1-dependent dysregulation of hematopoietic stem cells differentiation towards macrophages. Nat. Commun. 9, 33 (2018).
Yang, X. et al. Epigenetic regulation of macrophage polarization by DNA methyltransferase 3b. Mol. Endocrinol. 28, 565–574 (2014).
Yang, Y. et al. PSTPIP2 connects DNA methylation to macrophage polarization in CCL4-induced mouse model of hepatic fibrosis. Oncogene 37, 6119–6135 (2018).
Zhang, Q. et al. Tet2 is required to resolve inflammation by recruiting Hdac2 to specifically repress IL-6. Nature 525, 389–393 (2015).
Marr, A. K. et al. Leishmania donovani infection causes distinct epigenetic DNA methylation changes in host macrophages. PLoS Pathog. 10, e1004419 (2014).
Cao, Q. et al. Inhibiting DNA Methylation by 5-Aza-2’-deoxycytidine ameliorates atherosclerosis through suppressing macrophage inflammation. Endocrinology 155, 4925–4938 (2014).
Daskalaki, M. G., Tsatsanis, C. & Kampranis, S. C. Histone methylation and acetylation in macrophages as a mechanism for regulation of inflammatory responses. J. Cell. Physiol. 233, 6495–6507 (2018).
Kruidenier, L. et al. A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response. Nature 488, 404–408 (2012).
Stender, J. D. et al. Control of proinflammatory gene programs by regulated trimethylation and demethylation of histone H4K20. Mol. Cell 48, 28–38 (2012).
Heinz, S. et al. Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol. Cell 38, 576–589 (2010).
Weinmann, A. S., Plevy, S. E. & Smale, S. T. Rapid and selective remodeling of a positioned nucleosome during the induction of IL-12 p40 transcription. Immunity 11, 665–675 (1999).
Hoeksema, M. A. & de Winther, M. P. Epigenetic regulation of monocyte and macrophage function. Antioxid. Redox Signal. 25, 758–774 (2016).
Digiacomo, G. et al. Prostaglandin E2 transactivates the colony-stimulating factor-1 receptor and synergizes with colony-stimulating factor-1 in the induction of macrophage migration via the mitogen-activated protein kinase ERK1/2. FASEB J. 29, 2545–2554 (2015).
Hoeksema, M. A. et al. Targeting macrophage histone deacetylase 3 stabilizes atherosclerotic lesions. EMBO Mol. Med. 6, 1124–1132 (2014).
Mullican, S. E. et al. Histone deacetylase 3 is an epigenomic brake in macrophage alternative activation. Genes Dev. 25, 2480–2488 (2011).
Galván-Peña, S. & O’Neill, L. A. Metabolic reprograming in macrophage polarization. Front. Immunol. 5, 420 (2014).
Haas, R. et al. Intermediates of metabolism: from bystanders to signalling molecules. Trends Biochem. Sci. 41, 460–471 (2016).
Martinez-Outschoorn, U. E. et al. Ketones and lactate increase cancer cell “stemness,” driving recurrence, metastasis and poor clinical outcome in breast cancer: achieving personalized medicine via Metabolo-Genomics. Cell Cycle 10, 1271–1286 (2011).
Zhang, D. et al. Metabolic regulation of gene expression by histone lactylation. Nature 574, 575–580 (2019).
Ratti, M. et al. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) as new tools for cancer therapy: first steps from bench to bedside. Target. Oncol. 15, 261–278 (2020).
Lin, C. C. et al. Terminal uridyltransferase 7 regulates TLR4-triggered inflammation by controlling Regnase-1 mRNA uridylation and degradation. Nat. Commun. 12, 3878 (2021).
Self-Fordham, J. B. et al. MicroRNA: dynamic regulators of macrophage polarization and plasticity. Front. Immunol. 8, 1062 (2017).
Yao, W. et al. Single cell RNA sequencing identifies a unique inflammatory macrophage subset as a druggable target for alleviating acute kidney injury. Adv. Sci. 9, e2103675 (2022).
Wajahat, M., Bracken, C. P. & Orang, A. Emerging functions for snoRNAs and snoRNA-derived fragments. Int. J. Mol. Sci. 22, 10193 (2021).
Das, S. et al. Noncoding RNAs in cardiovascular disease: current knowledge, tools and technologies for investigation, and future directions: a scientific statement from the American Heart Association. Circ. Genom. Precis. Med. 13, e000062 (2020).
Sato, M. et al. The lncRNA Caren antagonizes heart failure by inactivating DNA damage response and activating mitochondrial biogenesis. Nat. Commun. 12, 2529 (2021).
Veremeyko, T. et al. IL-4/IL-13-dependent and independent expression of miR-124 and its contribution to M2 phenotype of monocytic cells in normal conditions and during allergic inflammation. PLoS ONE 8, e81774 (2013).
Nucera, S. et al. miRNA-126 orchestrates an oncogenic program in B cell precursor acute lymphoblastic leukemia. Cancer Cell. 29, 905–921 (2016).
Yin, J. et al. Pentraxin 3 regulated by miR-224-5p modulates macrophage reprogramming and exacerbates osteoarthritis associated synovitis by targeting CD32. Cell Death Dis. 13, 567 (2022).
Ma, W. T., Gao, F., Gu, K. & Chen, D. K. The role of monocytes and macrophages in autoimmune diseases: a comprehensive review. Front. Immunol. 10, 1140 (2019).
Malkiel, S. et al. Plasma cell differentiation pathways in systemic lupus erythematosus. Front. Immunol. 9, 427 (2018).
Katsiari, C. G. et al. Aberrant expression of the costimulatory molecule CD40 ligand on monocytes from patients with systemic lupus erythematosus. Clin. Immunol. 103, 54–62 (2002).
Harigai, M. et al. Responsiveness of peripheral blood B cells to recombinant CD40 ligand in patients with systemic lupus erythematosus. Lupus 8, 227–233 (1999).
Higuchi, T. et al. Cutting edge: ectopic expression of CD40 ligand on B cells induces lupus-like autoimmune disease. J. Immunol. 168, 9–12 (2002).
Wang, X. et al. Effects of anti-CD154 treatment on B cells in murine systemic lupus erythematosus. Arthritis Rheum. 48, 495–506 (2003).
Blanco, P. et al. Induction of dendritic cell differentiation by IFN-alpha in systemic lupus erythematosus. Science 294, 1540–1543 (2001).
Alivernini, S. et al. Distinct synovial tissue macrophage subsets regulate inflammation and remission in rheumatoid arthritis. Nat. Med. 26, 1295–1306 (2020).
Zhou, S., Lu, H. & Xiong, M. Identifying immune cell infiltration and effective diagnostic biomarkers in rheumatoid arthritis by bioinformatics analysis. Front. Immunol. 12, 726747 (2021).
Volkmann, E. R., Andréasson, K. & Smith, V. Systemic sclerosis. Lancet 401, 304–318 (2023).
Allanore, Y. et al. Systemic sclerosis. Nat. Rev. Dis. Prim. 1, 15002 (2015).
Lescoat, A., Lecureur, V. & Varga, J. Contribution of monocytes and macrophages to the pathogenesis of systemic sclerosis: recent insights and therapeutic implications. Curr. Opin. Rheumatol. 33, 463–470 (2021).
Ishikawa, O. & Ishikawa, H. Macrophage infiltration in the skin of patients with systemic sclerosis. J. Rheumatol. 19, 1202–1206 (1992).
Hinchcliff, M. et al. Mycophenolate mofetil treatment of systemic sclerosis reduces myeloid cell numbers and attenuates the inflammatory gene signature in skin. J. Invest. Dermatol. 138, 1301–1310 (2018).
Martinez, F. O. & Gordon, S. The evolution of our understanding of macrophages and translation of findings toward the clinic. Expert. Rev. Clin. Immunol. 11, 5–13 (2015).
Jaguin, M., Fardel, O. & Lecureur, V. AhR-dependent secretion of PDGF-BB by human classically activated macrophages exposed to DEP extracts stimulates lung fibroblast proliferation. Toxicol. Appl. Pharmacol. 285, 170–178 (2015).
Gao, X. et al. Osteopontin links myeloid activation and disease progression in systemic sclerosis. Cell Rep. Med. 1, 100140 (2020).
Morse, C. et al. Proliferating SPP1/MERTK-expressing macrophages in idiopathic pulmonary fibrosis. Eur. Respir. J. 54, 1802441 (2019).
Higashi-Kuwata, N. et al. Characterization of monocyte/macrophage subsets in the skin and peripheral blood derived from patients with systemic sclerosis. Arthritis Res. Ther. 12, R128 (2010).
Christmann, R. B. et al. Association of Interferon- and transforming growth factor β-regulated genes and macrophage activation with systemic sclerosis-related progressive lung fibrosis. Arthritis Rheumatol. 66, 714–725 (2014).
Soldano, S. et al. Increase in circulating cells coexpressing M1 and M2 macrophage surface markers in patients with systemic sclerosis. Ann. Rheum. Dis. 77, 1842–1845 (2018).
Li, X. et al. Harnessing tumor-associated macrophages as aids for cancer immunotherapy. Mol. Cancer 18, 177 (2019).
Hoeffel, G. & Ginhoux, F. Ontogeny of tissue-resident macrophages. Front. Immunol. 6, 486 (2015).
Sawa-Wejksza, K. & Kandefer-Szerszeń, M. Tumor-associated macrophages as target for antitumor therapy. Arch. Immunol. Ther. Exp. 66, 97–111 (2018).
Tong, N. et al. Tumor associated macrophages, as the dominant immune cells, are an indispensable target for immunologically cold tumor-glioma therapy? Front. Cell Dev. Biol. 9, 706286 (2021).
Lin, Y., Xu, J. & Lan, H. Tumor-associated macrophages in tumor metastasis: biological roles and clinical therapeutic applications. J. Hematol. Oncol. 12, 76 (2019).
DeNardo, D. G. & Ruffell, B. Macrophages as regulators of tumour immunity and immunotherapy. Nat. Rev. Immunol. 19, 369–382 (2019).
Greten, F. R. & Grivennikov, S. I. Inflammation and cancer: triggers, mechanisms, and consequences. Immunity 51, 27–41 (2019).
Poh, A. R. & Ernst, M. Targeting macrophages in cancer: from bench to bedside. Front. Oncol. 8, 49 (2018).
Cook, R. S. et al. MerTK inhibition in tumor leukocytes decreases tumor growth and metastasis. J. Clin. Invest. 123, 3231–3242 (2013).
Xia, L. et al. Role of the NFκB-signaling pathway in cancer. Onco Targets Ther. 11, 2063–2073 (2018).
Thomas, S. J., Snowden, J. A., Zeidler, M. P. & Danson, S. J. The role of JAK/STAT signalling in the pathogenesis, prognosis and treatment of solid tumours. Br. J. Cancer 113, 365–371 (2015).
Baker, K. J., Houston, A. & Brint, E. IL-1 family members in cancer; two sides to every story. Front. Immunol. 10, 1197 (2019).
Grivennikov, S. I., Greten, F. R. & Karin, M. Immunity, inflammation, and cancer. Cell 140, 883–899 (2010).
Coussens, L. M. & Werb, Z. Inflammation and cancer. Nature 420, 860–867 (2002).
Oh, S. A. & Li, M. O. TGF-β: guardian of T cell function. J. Immunol. 191, 3973–3979 (2013).
Santarpia, M. & Karachaliou, N. Tumor immune microenvironment characterization and response to anti-PD-1 therapy. Cancer Biol. Med. 12, 74–78 (2015).
Buchbinder, E. I. & Desai, A. CTLA-4 and PD-1 pathways: similarities, differences, and implications of their inhibition. Am. J. Clin. Oncol. 39, 98–106 (2016).
Hao, Z. et al. Landscape of Myeloid-derived Suppressor Cell in Tumor Immunotherapy. Biomark. Res. 9, 77 (2021).
Kapor, S. & Santibanez, J. F. Myeloid-derived suppressor cells and mesenchymal stem/stromal cells in myeloid malignancies. J. Clin. Med. 10, 2788 (2021).
Noy, R. & Pollard, J. W. Tumor-associated macrophages: from mechanisms to therapy. Immunity 41, 49–61 (2014).
Liu, F. et al. Microenvironment characterization and multi-omics signatures related to prognosis and immunotherapy response of hepatocellular carcinoma. Exp. Hematol. Oncol. 9, 10 (2020).
Eisinger, S. et al. Targeting a scavenger receptor on tumor-associated macrophages activates tumor cell killing by natural killer cells. Proc. Natl Acad. Sci. USA 117, 32005–32016 (2020).
Petty, A. J. et al. Hedgehog signaling promotes tumor-associated macrophage polarization to suppress intratumoral CD8 + T cell recruitment. J. Clin. Invest. 129, 5151–5162 (2019).
Xi, J. et al. miR-21 depletion in macrophages promotes tumoricidal polarization and enhances PD-1 immunotherapy. Oncogene 37, 3151–3165 (2018).
Ying, H. et al. MiR-127 modulates macrophage polarization and promotes lung inflammation and injury by activating the JNK pathway. J. Immunol. 194, 1239–1251 (2015).
Tu, J. et al. MicroRNA-22 represses glioma development via activation of macrophage-mediated innate and adaptive immune responses. Oncogene 41, 2444–2457 (2022).
Ma, C. et al. miR-182 targeting reprograms tumor-associated macrophages and limits breast cancer progression. Proc. Natl Acad. Sci. USA 119, e2114006119 (2022).
Squadrito, M. L., Etzrodt, M., De Palma, M. & Pittet, M. J. MicroRNA-mediated control of macrophages and its implications for cancer. Trends Immunol. 34, 350–359 (2013).
Ying, X. et al. Epithelial ovarian cancer-secreted exosomal miR-222-3p induces polarization of tumor-associated macrophages. Oncotarget 7, 43076–43087 (2016).
Balkwill, F. & Mantovani, A. Inflammation and cancer: back to Virchow? Lancet 357, 539–545 (2001).
Aggarwal, B. B., Vijayalekshmi, R. V. & Sung, B. Targeting inflammatory pathways for prevention and therapy of cancer: short-term friend, long-term foe. Clin. Cancer Res. 15, 425–430 (2009).
Balkwill, F. R. & Mantovani, A. Cancer-related inflammation: common themes and therapeutic opportunities. Semin. Cancer Biol. 22, 33–40 (2012).
Crusz, S. M. & Balkwill, F. R. Inflammation and cancer: advances and new agents. Nat. Rev. Clin. Oncol. 12, 584–596 (2015).
Cassetta, L. & Pollard, J. W. Targeting macrophages: therapeutic approaches in cancer. Nat. Rev. Drug Discov. 17, 887–904 (2018).
Grivennikov, S. I. et al. Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth. Nature 491, 254–258 (2012).
Kong, L. et al. Deletion of interleukin-6 in monocytes/macrophages suppresses the initiation of hepatocellular carcinoma in mice. J. Exp. Clin. Cancer Res. 35, 131 (2016).
Pastushenko, I. & Blanpain, C. EMT transition states during tumor progression and metastasis. Trends Cell Biol. 29, 212–226 (2019).
Yeung, K. T. & Yang, J. Epithelial-mesenchymal transition in tumor metastasis. Mol. Oncol. 11, 28–39 (2017).
Chen, Y., Tan, W. & Wang, C. Tumor-associated macrophage-derived cytokines enhance cancer stem-like characteristics through epithelial-mesenchymal transition. Onco Targets Ther. 11, 3817–3826 (2018).
Wei, C. et al. Crosstalk between cancer cells and tumor associated macrophages is required for mesenchymal circulating tumor cell-mediated colorectal cancer metastasis. Mol. Cancer 18, 64 (2019).
Tu, W. et al. TCF4 enhances hepatic metastasis of colorectal cancer by regulating tumor-associated macrophage via CCL2/CCR2 signaling. Cell Death Dis. 12, 882 (2021).
Lee, S. et al. Tumor-associated macrophages secrete CCL2 and induce the invasive phenotype of human breast epithelial cells through upregulation of ERO1-α and MMP-9. Cancer Lett. 437, 25–34 (2018).
Huang, R. et al. CCL5 derived from tumor-associated macrophages promotes prostate cancer stem cells and metastasis via activating β-catenin/STAT3 signaling. Cell Death Dis. 11, 234 (2020).
Nie, Y. et al. Breast phyllodes tumors recruit and repolarize tumor-associated macrophages via secreting CCL5 to promote malignant progression, which can be inhibited by CCR5 inhibition therapy. Clin. Cancer Res. 25, 3873–3886 (2019).
Lan, Q. et al. CCL26 participates in the PRL-3-induced promotion of colorectal cancer invasion by stimulating tumor-associated macrophage infiltration. Mol. Cancer Ther. 17, 276–289 (2018).
Guo, Z. et al. M2 macrophages promote NSCLC metastasis by upregulating CRYAB. Cell Death Dis. 10, 377 (2019).
Gao, L. et al. Tumor associated macrophages induce epithelial to mesenchymal transition via the EGFR/ERK1/2 pathway in head and neck squamous cell carcinoma. Oncol. Rep. 40, 2558–2572 (2018).
Geng, B. et al. Chitinase 3-like 1-CD44 interaction promotes metastasis and epithelial-to-mesenchymal transition through β-catenin/Erk/Akt signaling in gastric cancer. J. Exp. Clin. Cancer Res. 37, 208 (2018).
Gil-Bernabé, A. M. et al. Recruitment of monocytes/macrophages by tissue factor-mediated coagulation is essential for metastatic cell survival and premetastatic niche establishment in mice. Blood 119, 3164–3175 (2012).
Kong, D. H. et al. Emerging roles of vascular cell adhesion molecule-1 (VCAM-1) in immunological disorders and cancer. Int. J. Mol. Sci. 19, 1057 (2018).
Kaplan, R. N. et al. VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 438, 820–827 (2005).
Thapa, B. & Lee, K. Metabolic influence on macrophage polarization and pathogenesis. BMB Rep. 52, 360–372 (2019).
Rapisarda, A. & Melillo, G. Overcoming disappointing results with antiangiogenic therapy by targeting hypoxia. Nat. Rev. Clin. Oncol. 9, 378–390 (2012).
Du, R. et al. HIF1alpha induces the recruitment of bone marrow-derived vascular modulatory cells to regulate tumor angiogenesis and invasion. Cancer Cell 13, 206–220 (2008).
Yin, M. et al. Tumor-associated macrophages drive spheroid formation during early transcoelomic metastasis of ovarian cancer. J. Clin. Invest. 126, 4157–4173 (2016).
Cui, X. et al. Hacking macrophage-associated immunosuppression for regulating glioblastoma angiogenesis. Biomaterials 161, 164–178 (2018).
Anghelina, M., Krishnan, P., Moldovan, L. & Moldovan, N. I. Monocytes and macrophages form branched cell columns in matrigel: implications for a role in neovascularization. Stem Cells Dev. 13, 665–676 (2004).
Zhang, M. et al. The lncRNA NEAT1 activates Wnt/β-catenin signaling and promotes colorectal cancer progression via interacting with DDX5. J. Hematol. Oncol. 11, 113 (2018).
Lin, J. B. et al. WNT7A/B promote choroidal neovascularization. Exp. Eye Res. 174, 107–112 (2018).
Dong, B. et al. MiRNA-mediated EMT and CSCs in cancer chemoresistance. Exp. Hematol. Oncol. 10, 12 (2021).
Wan, S. et al. Tumor-associated macrophages produce interleukin 6 and signal via STAT3 to promote expansion of human hepatocellular carcinoma stem cells. Gastroenterology 147, 1393–1404 (2014).
Li, X. et al. CXCL12/CXCR4 pathway orchestrates CSC-like properties by CAF recruited tumor associated macrophage in OSCC. Exp. Cell Res. 378, 131–138 (2019).
Gomez, K. E. et al. Cancer cell CD44 mediates macrophage/monocyte-driven regulation of head and neck cancer stem cells. Cancer Res. 80, 4185–4198 (2020).
Xu, H. et al. CD44 as a tumor biomarker and therapeutic target. Exp. Hematol. Oncol. 9, 36 (2020).
Luo, S. et al. Macrophages are a double-edged sword: molecular crosstalk between tumor-associated macrophages and cancer stem cells. Biomolecules 12, 850 (2022).
Wei, R. et al. S100 calcium-binding protein A9 from tumor-associated macrophage enhances cancer stem cell-like properties of hepatocellular carcinoma. Int. J. Cancer 148, 1233–1244 (2021).
Wei, X. et al. Tumor-associated macrophages increase the proportion of cancer stem cells in lymphoma by secreting pleiotrophin. Am. J. Transl. Res. 11, 6393–6402 (2019).
Zhang, X. et al. CCL8 secreted by tumor-associated macrophages promotes invasion and stemness of glioblastoma cells via ERK1/2 signaling. Lab. Invest. 100, 619–629 (2020).
Chen, Y. et al. TNF-α derived from M2 tumor-associated macrophages promotes epithelial-mesenchymal transition and cancer stemness through the Wnt/β-catenin pathway in SMMC-7721 hepatocellular carcinoma cells. Exp. Cell Res. 378, 41–50 (2019).
Christensen, K., Doblhammer, G., Rau, R. & Vaupel, J. W. Ageing populations: the challenges ahead. Lancet 374, 1196–1208 (2009).
Duong, L. et al. Macrophage function in the elderly and impact on injury repair and cancer. Immun. Ageing 18, 4 (2021).
Gomez, C. R., Nomellini, V., Faunce, D. E. & Kovacs, E. J. Innate immunity and aging. Exp. Gerontol. 43, 718–728 (2008).
Jackaman, C. et al. Aging and cancer: the role of macrophages and neutrophils. Ageing Res. Rev. 36, 105–116 (2017).
Fontana, L. et al. Aging promotes the development of diet-induced murine steatohepatitis but not steatosis. Hepatology 57, 995–1004 (2013).
Linton, P. J. & Thoman, M. L. Immunosenescence in monocytes, macrophages, and dendritic cells: lessons learned from the lung and heart. Immunol. Lett. 162, 290–297 (2014).
van Beek, A. A. et al. Metabolic alterations in aging macrophages: ingredients for inflammaging? Trends Immunol. 40, 113–127 (2019).
Baker, D. J. et al. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature 479, 232–236 (2011).
Mosteiro, L. et al. Tissue damage and senescence provide critical signals for cellular reprogramming in vivo. Science 354, aaf4445 (2016).
Covarrubias, A. J. et al. Senescent cells promote tissue NAD(+) decline during ageing via the activation of CD38(+) macrophages. Nat. Metab. 2, 1265–1283 (2020).
Elder, S. S. & Emmerson, E. Senescent cells and macrophages: key players for regeneration? Open Biol. 10, 200309 (2020).
Ritschka, B. et al. The senescence-associated secretory phenotype induces cellular plasticity and tissue regeneration. Genes Dev. 31, 172–183 (2017).
Hickson, L. J. et al. Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease. EBioMedicine 47, 446–456 (2019).
Montgomery, R. R. & Shaw, A. C. Paradoxical changes in innate immunity in aging: recent progress and new directions. J. Leukoc. Biol. 98, 937–943 (2015).
Majeti, R. et al. CD47 is an adverse prognostic factor and therapeutic antibody target on human acute myeloid leukemia stem cells. Cell 138, 286–299 (2009).
Willingham, S. B. et al. The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors. Proc. Natl Acad. Sci. USA 109, 6662–6667 (2012).
Weiskopf, K. et al. CD47-blocking immunotherapies stimulate macrophage-mediated destruction of small-cell lung cancer. J. Clin. Invest. 126, 2610–2620 (2016).
Barkal, A. A. et al. Engagement of MHC class I by the inhibitory receptor LILRB1 suppresses macrophages and is a target of cancer immunotherapy. Nat. Immunol. 19, 76–84 (2018).
Wang, D., Dai, W. & Wang, J. A cell-specific nuclear factor-kappa B-activating gene expression strategy for delivering cancer immunotherapy. Hum. Gene Ther. 30, 471–484 (2019).
Cheng, L., Wang, Y. & Huang, L. Exosomes from M1-polarized macrophages potentiate the cancer vaccine by creating a pro-inflammatory microenvironment in the lymph node. Mol. Ther. 25, 1665–1675 (2017).
Xu, G. et al. Listeria-based hepatocellular carcinoma vaccine facilitates anti-PD-1 therapy by regulating macrophage polarization. Oncogene 39, 1429–1444 (2020).
Mantovani, A. et al. Tumour-associated macrophages as treatment targets in oncology. Nat. Rev. Clin. Oncol. 14, 399–416 (2017).
Wynn, T. A., Chawla, A. & Pollard, J. W. Macrophage biology in development, homeostasis and disease. Nature 496, 445–455 (2013).
Ring, N. G. et al. Anti-SIRPα antibody immunotherapy enhances neutrophil and macrophage antitumor activity. Proc. Natl Acad. Sci. USA 114, E10578–e10585 (2017).
Pathria, P., Louis, T. L. & Varner, J. A. Targeting tumor-associated macrophages in cancer. Trends Immunol. 40, 310–327 (2019).
Takenaka, M. C. et al. Control of tumor-associated macrophages and T cells in glioblastoma via AHR and CD39. Nat. Neurosci. 22, 729–740 (2019).
Klichinsky, M. et al. Human chimeric antigen receptor macrophages for cancer immunotherapy. Nat. Biotechnol. 38, 947–953 (2020).
Semiglazov, V. F. et al. Phase 2 randomized trial of primary endocrine therapy versus chemotherapy in postmenopausal patients with estrogen receptor-positive breast cancer. Cancer 110, 244–254 (2007).
Hughes, R. et al. Perivascular M2 macrophages stimulate tumor relapse after chemotherapy. Cancer Res. 75, 3479–3491 (2015).
Larionova, I. et al. Interaction of tumor-associated macrophages and cancer chemotherapy. Oncoimmunology 8, 1596004 (2019).
Mantovani, A. & Allavena, P. The interaction of anticancer therapies with tumor-associated macrophages. J. Exp. Med. 212, 435–445 (2015).
Sugimura, K. et al. High infiltration of tumor-associated macrophages is associated with a poor response to chemotherapy and poor prognosis of patients undergoing neoadjuvant chemotherapy for esophageal cancer. J. Surg. Oncol. 111, 752–759 (2015).
Shree, T. et al. Macrophages and cathepsin proteases blunt chemotherapeutic response in breast cancer. Genes Dev. 25, 2465–2479 (2011).
Germano, G. et al. Role of macrophage targeting in the antitumor activity of trabectedin. Cancer Cell 23, 249–262 (2013).
Castrellon, A. B., Pidhorecky, I., Valero, V. & Raez, L. E. The role of carboplatin in the neoadjuvant chemotherapy treatment of triple negative breast cancer. Oncol. Rev. 11, 324 (2017).
Su, Y. W. et al. A single institution experience of incorporation of cisplatin into adjuvant chemotherapy for patients with triple-negative breast cancer of unknown BRCA mutation status. Clin. Med. Insights Oncol. 12, 1179554918794672 (2018).
Wang, B. et al. Association of intra-tumoral infiltrating macrophages and regulatory T cells is an independent prognostic factor in gastric cancer after radical resection. Ann. Surg. Oncol. 18, 2585–2593 (2011).
Malesci, A. et al. Tumor-associated macrophages and response to 5-fluorouracil adjuvant therapy in stage III colorectal cancer. Oncoimmunology 6, e1342918 (2017).
Di Caro, G. et al. Dual prognostic significance of tumour-associated macrophages in human pancreatic adenocarcinoma treated or untreated with chemotherapy. Gut 65, 1710–1720 (2016).
Ma, J. et al. Tumor-associated macrophage-derived CCL5 promotes chemotherapy resistance and metastasis in prostatic cancer. Cell Biol. Int. 45, 2054–2062 (2021).
Guan, W. et al. Tumor-associated macrophage promotes the survival of cancer cells upon docetaxel chemotherapy via the CSF1/CSF1R-CXCL12/CXCR4 axis in castration-resistant prostate cancer. Genes 12, 773 (2021).
Huang, L., Jiang, S. & Shi, Y. Tyrosine kinase inhibitors for solid tumors in the past 20 years (2001-2020). J. Hematol. Oncol. 13, 143 (2020).
Chung, F. T. et al. Tumor-associated macrophages correlate with response to epidermal growth factor receptor-tyrosine kinase inhibitors in advanced non-small cell lung cancer. Int. J. Cancer 131, E227–E235 (2012).
Timaner, M. et al. Dequalinium blocks macrophage-induced metastasis following local radiation. Oncotarget 6, 27537–27554 (2015).
Stafford, J. H. et al. Colony stimulating factor 1 receptor inhibition delays recurrence of glioblastoma after radiation by altering myeloid cell recruitment and polarization. Neuro Oncol. 18, 797–806 (2016).
Rahal, O. M. et al. Blocking interleukin (IL)4- and IL13-mediated phosphorylation of STAT6 (Tyr641) decreases M2 polarization of macrophages and protects against macrophage-mediated radioresistance of inflammatory breast cancer. Int. J. Radiat. Oncol. Biol. Phys. 100, 1034–1043 (2018).
Ager, E. I. et al. Blockade of MMP14 activity in murine breast carcinomas: implications for macrophages, vessels, and radiotherapy. J. Natl. Cancer Inst. 107, djv017 (2015).
Aehnlich, P. et al. TAM receptor inhibition-implications for cancer and the immune system. Cancers 13, 1195 (2021).
Wynn, T. A. & Vannella, K. M. Macrophages in tissue repair, regeneration, and fibrosis. Immunity 44, 450–462 (2016).
Damanik, F. F. R. et al. Long-term controlled growth factor release using layer-by-layer assembly for the development of in vivo tissue-engineered blood vessels. ACS Appl. Mater. Interfaces 14, 28591–28603 (2022).
Campbell, L. et al. Local arginase 1 activity is required for cutaneous wound healing. J. Invest. Dermatol. 133, 2461–2470 (2013).
Kratochvill, F. et al. TNF counterbalances the emergence of M2 tumor macrophages. Cell Rep. 12, 1902–1914 (2015).
Ostuni, R., Kratochvill, F., Murray, P. J. & Natoli, G. Macrophages and cancer: from mechanisms to therapeutic implications. Trends Immunol. 36, 229–239 (2015).
Xiang, X., Wang, J., Lu, D. & Xu, X. Targeting tumor-associated macrophages to synergize tumor immunotherapy. Signal Transduct. Target Ther. 6, 75 (2021).
Van Acker, H. H. et al. Bisphosphonates for cancer treatment: mechanisms of action and lessons from clinical trials. Pharmacol. Ther. 158, 24–40 (2016).
Zhang, W. et al. Depletion of tumor-associated macrophages enhances the effect of sorafenib in metastatic liver cancer models by antimetastatic and antiangiogenic effects. Clin. Cancer Res. 16, 3420–3430 (2010).
Giraudo, E., Inoue, M. & Hanahan, D. An amino-bisphosphonate targets MMP-9-expressing macrophages and angiogenesis to impair cervical carcinogenesis. J. Clin. Invest. 114, 623–633 (2004).
Martin, C. K. et al. Zoledronic acid reduces bone loss and tumor growth in an orthotopic xenograft model of osteolytic oral squamous cell carcinoma. Cancer Res. 70, 8607–8616 (2010).
Pittet, M. J., Michielin, O. & Migliorini, D. Clinical relevance of tumour-associated macrophages. Nat. Rev. Clin. Oncol. 19, 402–421 (2022).
Chao, M. P., Weissman, I. L. & Majeti, R. The CD47-SIRPα pathway in cancer immune evasion and potential therapeutic implications. Curr. Opin. Immunol. 24, 225–232 (2012).
Xiao, Z. et al. Antibody mediated therapy targeting CD47 inhibits tumor progression of hepatocellular carcinoma. Cancer Lett. 360, 302–309 (2015).
Sockolosky, J. T. et al. Durable antitumor responses to CD47 blockade require adaptive immune stimulation. Proc. Natl Acad. Sci. USA 113, E2646–E2654 (2016).
Escamilla, J. et al. CSF1 receptor targeting in prostate cancer reverses macrophage-mediated resistance to androgen blockade therapy. Cancer Res. 75, 950–962 (2015).
Mok, S. et al. Inhibition of CSF-1 receptor improves the antitumor efficacy of adoptive cell transfer immunotherapy. Cancer Res. 74, 153–161 (2014).
Zheng, W. & Pollard, J. W. Inhibiting macrophage PI3Kγ to enhance immunotherapy. Cell Res. 26, 1267–1268 (2016).
Rodriguez-Garcia, A. et al. CAR-T cell-mediated depletion of immunosuppressive tumor-associated macrophages promotes endogenous antitumor immunity and augments adoptive immunotherapy. Nat. Commun. 12, 877 (2021).
Xia, Y. et al. Engineering macrophages for cancer immunotherapy and drug delivery. Adv. Mater. 32, e2002054 (2020).
Zhang, L. et al. Pluripotent stem cell-derived CAR-macrophage cells with antigen-dependent anti-cancer cell functions. J. Hematol. Oncol. 13, 153 (2020).
Kang, M. et al. Nanocomplex-mediated in vivo programming to chimeric antigen receptor-M1 macrophages for cancer therapy. Adv. Mater. 33, e2103258 (2021).
Ramelyte, E. et al. Oncolytic virotherapy-mediated anti-tumor response: a single-cell perspective. Cancer Cell. 39, 394–406.e394 (2021).
Desjardins, A. et al. Recurrent glioblastoma treated with recombinant poliovirus. N. Engl. J. Med. 379, 150–161 (2018).
Feng, N. et al. Treating autoimmune inflammatory diseases with an siERN1-nanoprodrug that mediates macrophage polarization and blocks toll-like receptor signaling. ACS Nano 15, 15874–15891 (2021).
Arai, S. et al. Apoptosis inhibitor of macrophage protein enhances intraluminal debris clearance and ameliorates acute kidney injury in mice. Nat. Med. 22, 183–193 (2016).
Phu, T. A. et al. IL-4 polarized human macrophage exosomes control cardiometabolic inflammation and diabetes in obesity. Mol. Ther. 30, 2274–2297 (2022).
Gao, H. et al. MiR-690 treatment causes decreased fibrosis and steatosis and restores specific Kupffer cell functions in NASH. Cell Metab. 34, 978–990.e974 (2022).
Hoang, T. N. et al. Baricitinib treatment resolves lower-airway macrophage inflammation and neutrophil recruitment in SARS-CoV-2-infected rhesus macaques. Cell 184, 460–475.e421 (2021).
Jaume, M. et al. Anti-severe acute respiratory syndrome coronavirus spike antibodies trigger infection of human immune cells via a pH- and cysteine protease-independent FcγR pathway. J. Virol. 85, 10582–10597 (2011).