Cited by 1,259Immune cells in cancerImmune responses and vaccinationsImmune Response and Inflammation

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Macrophage Polarization Comes of Age

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Mantovani,, Alberto, Sica,, Antonio, Locati, Massimo·2005·Immunity

DOI 10.1016/j.immuni.2005.10.001

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Abstract

Functional polarization of macrophages into M1 or M2 cells is an operationally useful, simplified conceptual framework describing the plasticity of mononuclear phagocytes. Genetic approaches have begun to shed new light on mechanisms underlying macrophage polarization and on the actual in vivo significance of polarized M2 cells ( [this issue of Immunity]).

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The chemokine system in diverse forms of macrophage activation and polarization
MANTOVANI, A., SICA, A., SOZZANI, S., ALLAVENA, P., VECCHI, A., & LOCATI, M. (2004) · Trends in Immunology · doi:10.1016/j.it.2004.09.015 · Cited by 6,534
Self-citation
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Fibrotic disease and the TH1/TH2 paradigm
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“If so, and despite the difficulties in extrapolating polarization marker expression between the human and murine systems (40), our results would be in agreement with the proposed role of PHDs as positive regulators of the LPS-induced inflammatory process (45) and the link between HIF1a induction and M1 polarization (6…”
BackgroundResult
Tumor-associated macrophages infiltrate plasmacytomas and can serve as cell carriers for oncolytic measles virotherapy of disseminated myeloma
Peng, K., Dogan, A., Vrana, J., Liu, C.-S., Ong, H., Kumar, S. K., Dispenzieri, A., Dietz, A., & Russell, S. (2009) · American journal of hematology/oncology · doi:10.1002/ajh.21444 · Cited by 64
“Macrophages are broadly divided into M1 and M2 subtypes [34].”
Background
Interleukin 13 receptor alpha 2 (IL13Rα2): Expression, signaling pathways and therapeutic applications in cancer
Jaén, M., Martín‐Regalado, Á., Bartolomé, R. A., Robles, J., & Casal, J. I. (2022) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2022.188802 · Cited by 65
The interplay between innate and adaptive immunity in cancer shapes the productivity of cancer immunosurveillance
Chang, R. B., & Beatty, G. L. (2020) · Journal of Leukocyte Biology · doi:10.1002/jlb.3mir0320-475r · Cited by 99
The Interplay of MicroRNAs in the Inflammatory Mechanisms Following Ischemic Stroke
Khoshnam, S. E., Winlow, W., & Farzaneh, M. (2017) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlx036 · Cited by 69
IRF5-mediated signaling and implications for SLE
Lazzari, E., & Jefferies, C. A. (2014) · Clinical Immunology · doi:10.1016/j.clim.2014.06.001 · Cited by 63
Innate Immunity, Decidual Cells, and Preeclampsia
Yeh, C.-C., Chao, K.-C., & Huang, S.-T. J. (2012) · Reproductive Sciences · doi:10.1177/1933719112450330 · Cited by 68
“Similar to the concept of Th1/Th2 polarization in effector T cell function, MFs are proposed to be categorized into either classically activated macrophage (M1) or alternatively activated macrophage (M2) subgroups according to their effector phenotypes in response to specific stimuli.(144,156,180) M1 MFs produce TNF-a…”
Background
Critical Roles for Macrophages in Islet Angiogenesis and Maintenance During Pancreatic Degeneration
Tessem, J. S., Jensen, J. N., Pelli, H., Dai, X.-M., Zong, X.-H., Stanley, E. R., Jensen, J. N., & DeGregori, J. V. (2008) · Diabetes · doi:10.2337/db07-1577 · Cited by 57
“expression of arginase1, mannose receptors, and IL-10 and its receptor, previously associated with TAMs and M2 macrophages, is increased during caerulein-induced pancreatitis and is known to promote and influence trophic macrophage functions (32).”
Background
Calycosin Preserves BDNF/TrkB Signaling and Reduces Post-Stroke Neurological Injury after Cerebral Ischemia by Reducing Accumulation of Hypertrophic and TNF-α-Containing Microglia in Rats
Hsu, C., Kuo, T., Liu, W., Chang, C., & Lin, H. (2020) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-019-09903-9 · Cited by 68
“Macrophages can also be classified into the following two groups: M1 (or hypertrophic) macrophages, which produce pro-inflammatory cytokines, chemokines, ROS, and NO; and M2 (ramified) macrophages, which produce antiinflammatory cytokines (Mantovani et al. 2005).”
MPGES-1-derived PGE2 suppresses CD80 expression on tumor-associated phagocytes to inhibit anti-tumor immune responses in breast cancer
Olesch, C., Sha, W., Angioni, C., Sha, L. K., Açaf, E., Patrignani, P., Jakobsson, P., Radeke, H. H., Grösch, S., Geißlinger, G., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.3581 · Cited by 64
“We conclude that PGE2 signaling alters polarization of human tumor-associated phagocytes independent of the M1/M2 paradigm [30].”
Activation of Thromboxane A2 Receptor (TP) Increases the Expression of Monocyte Chemoattractant Protein -1 (MCP-1)/Chemokine (C-C motif) Ligand 2 (CCL2) and Recruits Macrophages to Promote Invasion of Lung Cancer Cells
Li, X., & Tai, H. (2013) · PLoS ONE · doi:10.1371/journal.pone.0054073 · Cited by 58
“High expression of IL-10 is one of the characteristic of M2 phenotype [49], thus this study suggested that these macrophages behaved as M2-polarized TAMs and thereafter promoted progression of NSCLC.”
Background
Myelin-phagocytosing macrophages modulate autoreactive T cell proliferation
Bogie, J. F. J., Stinissen, P., Hellings, N., & Hendriks, J. J. A. (2011) · Journal of Neuroinflammation · doi:10.1186/1742-2094-8-85 · Cited by 62
“Macrophages can adopt divergent phenotypes based on specific stimuli in their microenvironment [74-77].”
Background
Bacterial CpG-DNA accelerates Alport glomerulosclerosis by inducing an M1 macrophage phenotype and tumor necrosis factor-α-mediated podocyte loss
Ryu, M., Kulkarni, O. P., Radomska, E., Miosge, N., Groß, O., & Anders, H. (2010) · Kidney International · doi:10.1038/ki.2010.373 · Cited by 61
Expression of Transient Receptor Potential C6 Channels in Human Lung Macrophages
Finney‐Hayward, T. K., Popa, M. O., Bahra, P., Li, S., Poll, C. T., Gosling, M., Nicholson, A. G., Russell, R. E. K., Kon, O. M., Járai, G., et al. (2009) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2008-0373oc · Cited by 62
Molecular Mechanisms in Spermatogenesis
Cheng, C.-Y. (2008) · Advances in experimental medicine and biology · doi:10.1007/978-0-387-09597-4 · Cited by 280
Tissue Iron Promotes Wound Repair via M2 Macrophage Polarization and the Chemokine (C-C Motif) Ligands 17 and 22
Wilkinson, H. N., Roberts, E. R., Stafford, A. R., Banyard, K. L., Matteucci, P. L., Mace, K. A., & Hardman, M. J. (2019) · American Journal Of Pathology · doi:10.1016/j.ajpath.2019.07.015 · Cited by 75
“244 245 246 247 scavenging of debris, bacteria, and proinflammatory cells; and they orchestrate reparative processes to allow wound resolution.(1) There is a clear existing association between iron and macrophages in the context of erythropoiesis.”
Background
Macrophage Heterogeneity: Relevance and Functional Implications in Atherosclerosis
Stöger, J. L., Goossens, P., & de Winther, M. P. J. (2010) · Current Vascular Pharmacology · doi:10.2174/157016110790886983 · Cited by 54
P22 virus-like particles as an effective antigen delivery nanoplatform for cancer immunotherapy
Li, W., Jing, Z., Wang, S., Li, Q., Xing, Y., Shi, H., Li, S., & Hong, Z. (2021) · Biomaterials · doi:10.1016/j.biomaterials.2021.120726 · Cited by 74
Tanshinone IIA prevents LPS-induced inflammatory responses in mice via inactivation of succinate dehydrogenase in macrophages
Liu, Q., Zhuang, Y., Song, X., Niu, Q., Sun, Q., Li, X., Li, N., Liu, B., Huang, F., & Qiu, Z. (2020) · Acta Pharmacologica Sinica · doi:10.1038/s41401-020-00535-x · Cited by 67
Macrophages Counteract Demyelination in a Mouse Model of Globoid Cell Leukodystrophy
Kondo, Y., Adams, J. M., Vanier, M. T., & Duncan, I. D. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.6344-10.2011 · Cited by 58
“The former includes iNOS, CD16, and CD86, and the latter includes arginase-1 and CD206 (Gordon, 2003; Mantovani et al., 2005; Popovich and Longbrake, 2008; Kigerl et al., 2009).”
Background
Protective Role of Interleukin-17 in Murine NKT Cell-Driven Acute Experimental Hepatitis
Wondimu, Z., Santodomingo-Garzón, T., Le, T. P., & Swain, M. G. (2010) · American Journal Of Pathology · doi:10.2353/ajpath.2010.100028 · Cited by 56
“Inflammatory, or M1 monocytes, predominantly produce IL-12 (but also TNF ) and express the surface marker Ly-6C and the chemokine receptor CCR2.”
Method
Coinfection with the Intestinal NematodeHeligmosomoides polygyrusMarkedly Reduces Hepatic Egg-Induced Immunopathology and Proinflammatory Cytokines in Mouse Models of Severe Schistosomiasis
Bazzone, L. E., Smith, P. M., Rutitzky, L. I., Shainheit, M. G., Urban, J. F., Setiawan, T., Blum, A. M., Weinstock, J. V., & Stadecker, M. J. (2008) · Infection and Immunity · doi:10.1128/iai.00673-08 · Cited by 60
“IL-4 is critical for the development of AAM (26, 40, 44), and IL-10 and TGF- are anti-inflammatory cytokines widely associated with Treg activity (3, 43, 71).”
Background
Identification of a distinct glucocorticosteroid-insensitive pulmonary macrophage phenotype in patients with chronic obstructive pulmonary disease.
Chana, K., Fenwick, P., Nicholson, A., Barnes, P., & Donnelly, L. (2014) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2013.08.044 · Cited by 60
Trophoblast-derived IL-6 serves as an important factor for normal pregnancy by activating Stat3-mediated M2 macrophages polarization.
Ding, J.-L., Yang, C.-G., Cheng, Y.-X., Wang, J.-Y., Zhang, S., Yan, S.-S., He, F., Yin, T., & Yang, J. (2020) · International Immunopharmacology · doi:10.1016/j.intimp.2020.106788 · Cited by 59
Macrophages in Colorectal Cancer Liver Metastases
Cortese, N., Soldani, C., Franceschini, B., Barbagallo, M., Marchesi, F., Torzilli, G., & Donadon, M. (2019) · Cancers · doi:10.3390/cancers11050633 · Cited by 63
Granulocyte colony-stimulating factor improves alternative activation of microglia under microenvironment of spinal cord injury.
Guo, Y., Zhang, H., Yang, J., Liu, S.-M., Bing, L.-J., Gao, J., & Hao, A.-J. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.01.047 · Cited by 59
“Mantovani et al. proposed that macrophages are divided into two types – classically activated macrophage and alternatively activated macrophage according to the different activation status and functioning (Mantovani et al., 2002, 2005).”
Background
Distinct Roles of Endothelial and Adipocyte Caveolin-1 in Macrophage Infiltration and Adipose Tissue Metabolic Activity
Briand, N., Lay, S. L., Sessa, W., Ferré, P., & Dugail, I. (2011) · Diabetes · doi:10.2337/db10-0856 · Cited by 59
“Adipose tissue is normally hosting a small number of resident macrophages, which display a reparative phenotype (M2 or alternative activation) (17), characterized by the expression of proteins implicated in tissue remodeling as arginase-1 (Arg-1), mannose receptor C type 2 (Mrc-2), or macrophage galactose N-acetyl-gal…”
Background
Matrix Metalloproteinases and Leukocyte Activation
Smigiel, K. S., & Parks, W. C. (2017) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2017.01.003 · Cited by 77
Epstein Barr Virus Interleukin 10 Suppresses Anti-inflammatory Phenotype in Human Monocytes
Jog, N. R., Chakravarty, E. F., Guthridge, J. M., & James, J. A. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02198 · Cited by 69
“Monocyte derived macrophages can be polarized into inflammatory and anti-inflammatory phenotypes (25).”
Background
Rett syndrome and other autism spectrum disorders—brain diseases of immune malfunction?
Derecki, N. C., Privman, E., & Kipnis, J. (2010) · Molecular Psychiatry · doi:10.1038/mp.2010.21 · Cited by 50
Effective induction of anti-tumor immune responses with oligomannose-coated liposome targeting to intraperitoneal phagocytic cells.
Ikehara, Y., Shiuchi, N., Kabata-Ikehara, S., Nakanishi, H., Yokoyama, N., Takagi, H., Nagata, T., Koide, Y., Kuzushima, K., Takahashi, T., et al. (2008) · Cancer Letters · doi:10.1016/j.canlet.2007.10.038 · Cited by 58
“M/ are now roughly categorized into M1 and M2 based on their functional properties, and several studies revealed that M1 and M2 promote type I and type II Th responses, respectively [27–29].”
Background
Role of CXCR3 Ligands in IL-7/IL-7Rα-Fc mediated antitumor activity in Lung Cancer
Andersson, Å., Srivastava, M., Harris-White, M., Huang, M., Zhu, L. X., Elashoff, D., Strieter, R., Dubinett, S., & Sharma, S. P. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-3346 · Cited by 57
Regulation of the microsomal prostaglandin E synthase-1 in polarized mononuclear phagocytes and its constitutive expression in neutrophils
Mosca, M., Polentarutti, N., Mangano, G., Apicella, C., Doni, A., Mancini, F., Bortoli, M. D., Coletta, I., Polenzani, L., Santoni, G., et al. (2007) · Journal of Leukocyte Biology · doi:10.1189/jlb.0906576 · Cited by 53
“M2 macrophages have immunoregulatory functions and promote tissue remodeling and repair [18, 19, 38].”
Background
Macrophage diversity in cardiac inflammation: A review
Barin, J. G., Rose, N. R., & Čiháková, D. (2012) · Immunobiology · doi:10.1016/j.imbio.2011.06.009 · Cited by 56
“These macrophage phenotypes are associated with immunosuppressive and angiogenic functions, elicited by tumors evading immune surveillance (33).”
Background
The density of macrophages in colorectal cancer is inversely correlated to TGF-β1 expression and patients’ survival
Gulubova, M. V., Ananiev, J. R., Yovchev, Y., Julianov, A. E., Karashmalakov, A. G., & Vlaykova, T. I. (2013) · Journal of Molecular Histology · doi:10.1007/s10735-013-9520-9 · Cited by 52
“To the opposite, M2 macrophages have poor antigen presenting capacity, have IL12 low , IL-10 high phenotype, suppress the inflammatory responses and Th1 adaptive immunity, actively scavenge debris, promote angiogenesis and tissue remodelling (Allavena et al. 2008; Mantovani et al. 2005).”
Influence of low oxygen tensions on macrophage polarization
Escribese, M. M., Casas, M., & Corbí, A. L. (2012) · Immunobiology · doi:10.1016/j.imbio.2012.07.002 · Cited by 69
STAT3: A Central Mediator of Pulmonary Fibrosis?
Prêle, C. M., Yao, E., O’Donoghue, R. J. J., Mutsaers, S. E., & Knight, D. A. (2012) · Proceedings of the American Thoracic Society · doi:10.1513/pats.201201-007aw · Cited by 54
Elevated PCNA+ tumor-associated macrophages in breast cancer are associated with early recurrence and non-Caucasian ethnicity
Mukhtar, R. A., Moore, A. P., Nseyo, O., Baehner, F. L., Au, A., Moore, D. H., Twomey, P. L., Campbell, M. J., & Esserman, L. J. (2011) · Breast Cancer Research and Treatment · doi:10.1007/s10549-011-1646-4 · Cited by 53
“Once thought to be a part of the host response to tumors, TAMs are now known to contribute to tumor growth by producing angiogenic factors, stromal breakdown factors, and suppressing adaptive immunity [23–27].”
Background
Endothelial-to-mesenchymal transition in systemic sclerosis
Benedetto, P. D., Ruscitti, P., Berardicurti, O., Vomero, M., Navarini, L., Dolo, V., Cipriani, P., & Giacomelli, R. (2021) · Clinical & Experimental Immunology · doi:10.1111/cei.13599 · Cited by 60
Mouse macrophage specific knockout of SIRT1 influences macrophage polarization and promotes angiotensin II-induced abdominal aortic aneurysm formation.
Zhang, Z.-Q., Xu, J., Liu, Y., Wang, T.-T., Pei, J.-F., Cheng, L.-Q., Hao, D.-L., Zhao, X., Chen, H.-Z., & Liu, D.-P. (2018) · Journal of genetics and genomics = Yi chuan xue bao · doi:10.1016/j.jgg.2018.01.002 · Cited by 55

Authors: Mantovani, Sica, & Locati, M.
Affiliations: University of Milan (IT)
Corresponding author: Mantovani,, Alberto
ORCID: Mantovani,, Alberto
Sica,, Antonio
Locati, Massimo
Venue: Immunity
Publisher: Elsevier BV
Published: 2005-10
Volume: 23
Issue: 4
Pages: 344-346
ISSN: 1074-7613 (ISSN-L)
DOI: 10.1016/j.immuni.2005.10.001
OpenAlex: W1986736465
Cited by: 1,259
References: 0
Citations by year: 2026: 41 · 2025: 60 · 2024: 58 · 2023: 54 · 2022: 70 · 2021: 65 · 2020: 68 · 2019: 58 · 2018: 57 · 2017: 70 · 2016: 67 · 2015: 64 · 2014: 85 · 2013: 89 · 2012: 80
FWCI: 9.96
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 2846 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Immunity (publishedVersion)
PubMed (publishedVersion)
Funders: Ministero dell’Istruzione, dell’Università e della Ricerca
Associazione Italiana per la Ricerca sul Cancro
European Commission
Ministero della Salute
Topics: Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords: macrophage polarization, M1 macrophages, M2 macrophages, mononuclear phagocytes, macrophage plasticity
MeSH terms: Cell Differentiation, Macrophages

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Macrophage Polarization Comes of Age

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