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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Gordon, S. (2003) · Nature Reviews Immunology · doi:10.1038/nri978 · Cited by 6,189
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Show all 0 references

Research works printed but not linked: 10

Dinarello, 2005, Blocking IL-1 in systemic inflammation, J. Exp. Med., 201, 1355, 10.1084/jem.20050640 · DOI
Duffield, 2005, Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair, J. Clin. Invest., 115, 56, 10.1172/JCI200522675 · DOI · Paper page
Fang, 2004, Lipopolysaccharide-induced macrophage inflammatory response is regulated by SHIP, J. Immunol., 173, 360, 10.4049/jimmunol.173.1.360 · DOI
Herbert, 2004, Alternative macrophage activation is essential for survival during schistosomiasis and downmodulates T helper 1 responses and immunopathology, Immunity, 20, 623, 10.1016/S1074-7613(04)00107-4 · DOI
Mantovani, 2002, Macrophage polarization: Tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes, Trends Immunol., 23, 549, 10.1016/S1471-4906(02)02302-5 · DOI · Paper page
Noel, 2004, Alternatively activated macrophages during parasite infections, Trends Parasitol., 20, 126, 10.1016/j.pt.2004.01.004 · DOI
Pull, 2005, Activated macrophages are an adaptive element of the colonic epithelial progenitor niche necessary for regenerative responses to injury, Proc. Natl. Acad. Sci. USA, 102, 99, 10.1073/pnas.0405979102 · DOI
Rauh, 2005, SHIP represses the generation of alternatively activated macrophages, Immunity, 24, 361, 10.1016/j.immuni.2005.09.003 · DOI
Scotton, 2005, Transcriptional profiling reveals complex regulation of the monocyte IL-1 beta system by IL-13, J. Immunol., 174, 834, 10.4049/jimmunol.174.2.834 · DOI
Zhu, 2004, Acidic mammalian chitinase in asthmatic Th2 inflammation and IL-13 pathway activation, Science, 304, 1678, 10.1126/science.1095336 · DOI

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BackgroundInfluential
IL-17-Producing Alveolar Macrophages Mediate Allergic Lung Inflammation Related to Asthma
Song, C., Luo, L., Zhang, L., Li, B., Liang, Z., Liu, G., Li, D., Zhang, G., Huang, B., & Feng, Z. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.9.6117 · Cited by 304
“Enhanced macrophage recruitment during asthmatic process may result in the accumulation of tissue macrophages, which are activated by Th2 cytokines, leading to Th2 polarized reaction and inflammation (32, 33).”
Background
Islet inflammation in type 2 diabetes and physiology
Eguchi, K., & Nagai, R. (2017) · Journal of Clinical Investigation · doi:10.1172/jci88877 · Cited by 374
Tissue‐resident macrophages: then and now
Davies, L. C., & Taylor, P. R. (2015) · Immunology · doi:10.1111/imm.12451 · Cited by 348
Tumor-associated Macrophages (TAM) and Inflammation in Colorectal Cancer
Erreni, M., Mantovani, A., & Allavena, P. (2010) · Cancer Microenvironment · doi:10.1007/s12307-010-0052-5 · Cited by 336
“IL-6 modulates the expression of chemokines and adhesion molecules thus suppressing neutrophil infiltration, promoting the accumulation of mononuclear leukocytes and leading to the resolution of acute inflammation and the activation of acquired immunity [72, 73].”
Background
CD36 tango in cancer: signaling pathways and functions
Wang, J., & Li, Y. (2019) · Theranostics · doi:10.7150/thno.36037 · Cited by 369
“Macrophages can polarize toward both M1 (classical) activation and M2 (alternative) activation [125].”
Background
Neurogenesis and Inflammation after Ischemic Stroke: What is Known and Where We Go from Here
Tobin, M. K., Bonds, J. A., Minshall, R. D., Pelligrino, D. A., Testai, F. D., & Lazarov, O. (2014) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2014.130 · Cited by 310
Understanding the Complexity of the Immune System during Pregnancy
Racicot, K. E., Kwon, J., Aldo, P. B., Silasi, M., & Mor, G. (2014) · American Journal of Reproductive Immunology · doi:10.1111/aji.12289 · Cited by 348
Crosstalk among Jak-STAT, Toll-like receptor, and ITAM-dependent pathways in macrophage activation
Hu, X., Chen, J., Wang, L., & Ivashkiv, L. B. (2007) · Journal of Leukocyte Biology · doi:10.1189/jlb.1206763 · Cited by 293
“[ 2 ]). M2 macrophages are also important for wound healing and tissue remodeling, which follow infection or tissue injury.”
Background
The Role of Tumor-Infiltrating Immune Cells and Chronic Inflammation at the Tumor Site on Cancer Development, Progression, and Prognosis: Emphasis on Non-small Cell Lung Cancer
Bremnes, R. M., Al-Shibli, K. I., Dønnem, T., Sirera, R., Al‐Saad, S., Andersen, S., Stenvold, H., Camps, C., & Busund, L. (2010) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e3182037b76 · Cited by 373
Immuno-subtyping of breast cancer reveals distinct myeloid cell profiles and immunotherapy resistance mechanisms
Kim, I. S., Gao, Y., Welte, T., Wang, H., Liu, J., Janghorban, M., Sheng, K., Niu, Y., Goldstein, A., Zhao, N., et al. (2019) · Nature Cell Biology · doi:10.1038/s41556-019-0373-7 · Cited by 340
The impact of ageing on monocytes and macrophages
De Maeyer, R. P. H., & Chambers, E. S. (2021) · Immunology Letters · doi:10.1016/j.imlet.2020.12.003 · Cited by 275
“their increased reactive oxygen species (ROS) production (40).”
Background
Polydopamine-mediated graphene oxide and nanohydroxyapatite-incorporated conductive scaffold with an immunomodulatory ability accelerates periodontal bone regeneration in diabetes
Li, Y., Yang, L., Hou, Y., Zhang, Z., Chen, M., Wang, M., Liu, J., Wang, J., Zhao, Z., Xie, C., et al. (2022) · Bioactive Materials · doi:10.1016/j.bioactmat.2022.03.021 · Cited by 283
“Macrophages affect inflammatory and tissue healing processes via two distinct polarization states: M1 macrophages that induce chronic inflammation and M2 macrophages that promote tissue healing and anti-inflammation [42,43].”
Background
Fats, inflammation and insulin resistance: insights to the role of macrophage and T-cell accumulation in adipose tissue
Harford, K. A., Reynolds, C. M., McGillicuddy, F. C., & Roche, H. M. (2011) · Proceedings of The Nutrition Society · doi:10.1017/s0029665111000565 · Cited by 309
“There are two broad macrophage populations((40)) (Fig.”
Microglia and monocyte-derived macrophages: functionally distinct populations that act in concert in CNS plasticity and repair
London, A., Cohen, M., & Schwartz, M. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00034 · Cited by 282
“…macrophages to an alternatively activated M2 phenotype associated with wound healing and immune resolution (Gordon, 2003; Gordon and Taylor, 2005; Mantovani et al., 2005; Mosser and Edwards, 2008; Auffray et al., 2009; Martinez et al., 2009; Gordon and Martinez, 2010; Sica and Mantovani, 2012).”
Background
Comparative analysis of RT-qPCR, flow cytometry, and Di-4-ANEPPDHQ fluorescence for distinguishing macrophages phenotypes
Siniyeh, A. A., Alshaer, W., Elzogheir, N., Al-Holi, M., Alqudah, D. A., Abuarqoub, D., & Kwiatek, J. M. (2025) · Biochemistry and Biophysics Reports · doi:10.1016/j.bbrep.2025.102225 · Cited by 280
“On the other side, anti-inflammatory signals like IL-4 and IL-13 originate M2 macrophages promoting tissue repair and resolution of inflammation [3,4].”
Cancer vaccines
Butterfield, L. H. (2015) · BMJ · doi:10.1136/bmj.h988 · Cited by 288
High-Resolution Transcriptome of Human Macrophages
Beyer, M., Mallmann, M. R., Xue, J., Staratschek‐Jox, A., Vorholt, D., Krebs, W., Sommer, D. D., Sander, J., Mertens, C., Niño‐Castro, A., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0045466 · Cited by 255
“2C) further demonstrated that the genes encoding for the surface molecules FCGR1A and FCGR1B (both representing CD64) and CD86, the cytokine/chemokine genes CXCL10, CXCL9, IL-1B, IL-6, CXCL11, TNF, IL-23A, and the genes encoding for the intracellular protein GBP1 were increased in M1-like macrophages, results similar…”
Result
IL-33/ST2 axis in inflammation and immunopathology
Milovanović, M., Volarević, V., Radosavljevic, G. D., Jovanović, I., Pejnovic, N. N., Arsenijević, N., & Lukić, M. L. (2012) · Immunologic Research · doi:10.1007/s12026-012-8283-9 · Cited by 266
Cellular and molecular pathways linking inflammation and cancer
Porta, C., Larghi, P., Rimoldi, M., Totaro, M. G., Allavena, P., Mantovani, A., & Sica, A. (2009) · Immunobiology · doi:10.1016/j.imbio.2009.06.014 · Cited by 262
“Indeed, in response to different microenvironmental signals macrophages can express different ‘‘polarized’’ functional programs (Mantovani et al. 2005).”
Regulation of macrophage function in tumors: the multifaceted role of NF-κB
Hagemann, T., Biswas, S. K., Lawrence, T., Sica, A., & Lewis, C. E. (2009) · Blood · doi:10.1182/blood-2008-12-172825 · Cited by 249
“It would be interesting to see if IKKβ or p50 are required for alternative activation of macrophages (as assessed by such markers as TGFβ, Fizz1, Ym1, Mgl2).(17,76,77) Neither Saccani and colleagues(47) nor Hagemann et al(46) have shown NF-κB regulates expression of M2 genes.”
Reversal of Hyperlipidemia With a Genetic Switch Favorably Affects the Content and Inflammatory State of Macrophages in Atherosclerotic Plaques
Feig, J. E., Parathath, S., Rong, J. X., Mick, S. L., Vengrenyuk, Y., Grauer, L., Young, S. G., & Fisher, E. A. A. (2011) · Circulation · doi:10.1161/circulationaha.110.984146 · Cited by 237
GM-CSF- and M-CSF-dependent macrophage phenotypes display differential dependence on Type I interferon signaling
Fleetwood, A. J., Dinh, H., Cook, A. D., Hertzog, P. J., & Hamilton, J. A. (2009) · Journal of Leukocyte Biology · doi:10.1189/jlb.1108702 · Cited by 312
“Mirroring the Th1/Th2 nomenclature, polarized macrophages are often referred to as M1 (classical activation) and M2 (alternative activation) cells, respectively [11, 12].”
Background
Macrophages, Chronic Inflammation, and Insulin Resistance
He, L., Meng, Y., He, S., Tan, X., Zhang, Y., Zhang, X., Wang, L., & Zheng, W. (2022) · Cells · doi:10.3390/cells11193001 · Cited by 286
“The PRRs can also recognize pathogenassociated molecular patterns (PAMPs) on pathogens and biological allergens, including LPS, peptidoglycan, and bacterial DNA [135,136].”
BackgroundInfluential
Impaired Cholesterol Efflux in Senescent Macrophages Promotes Age-Related Macular Degeneration
Sene, A., Khan, A. A., Cox, D., Nakamura, R. E. I., Santeford, A., Kim, B. M., Sidhu, R., Onken, M. D., Harbour, J. W., Hagbi-Levi, S., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.03.009 · Cited by 277
“Recent studies have demonstrated that macrophage polarization can play a pivotal role in determining their ultimate effector functions, including their ability to regulate angiogenesis (Apte et al., 2006; Kelly et al., 2007; Mantovani et al., 2005; Mosser, 2003).”
The promotion of a constructive macrophage phenotype by solubilized extracellular matrix
Sicari, B. M., Dziki, J. L., Siu, B. F., Medberry, C. J., Dearth, C. L., & Badylak, S. F. (2014) · Biomaterials · doi:10.1016/j.biomaterials.2014.06.060 · Cited by 255
Tumor infiltrating immune cells in gliomas and meningiomas
Domingues, P., González-Tablas, M., Otero, Á., Pascual, D., Miranda, D., Ruíz, L., Sousa, P., Ciudad, J., Gonçalves, J. M., Lopes, M. C., et al. (2015) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2015.07.019 · Cited by 309
Targeting GM-CSF in inflammatory diseases
Wicks, I. P., & Roberts, A. W. (2015) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2015.161 · Cited by 271
Diverse macrophages polarization in tumor microenvironment
Rhee, I. (2016) · Archives of Pharmacal Research · doi:10.1007/s12272-016-0820-y · Cited by 295
“Macrophages generate different populations in response to these innate or adaptive signals (Mantovani et al. 2005; Martinez et al. 2008).”
Background
Surface modification of nanoparticles enables selective evasion of phagocytic clearance by distinct macrophage phenotypes
Qie, Y., Yuan, H., Roemeling, C. A. V., Chen, Y., Liu, X., Shih, K. D., Knight, J. A., Tun, H. W., Wharen, R. E., Jiang, W., et al. (2016) · Scientific Reports · doi:10.1038/srep26269 · Cited by 263
Macrophages—Key cells in the response to wear debris from joint replacements
Nich, C., Takakubo, Y., Pajarinen, J., Ainola, M., Salem, A., Sillat, T., Rao, A. J., Raška, M., Tamaki, Y., Takagi, M., et al. (2013) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.34599 · Cited by 257

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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