New insights into M1/M2 macrophages: key modulators in cancer progression
Open accessAbstract
Infiltration of macrophages in and around tumor nest represents one of the most crucial hallmarks during tumor progression. The mutual interactions with tumor cells and stromal microenvironment contribute to phenotypically polarization of tumor associated macrophages. Macrophages consist of at least two subgroups, M1 and M2. M1 phenotype macrophages are tumor-resistant due to intrinsic phagocytosis and enhanced antitumor inflammatory reactions. Contrastingly, M2 are endowed with a repertoire of tumor-promoting capabilities involving immuno-suppression, angiogenesis and neovascularization, as well as stromal activation and remodeling. The functional signature of M2 incorporates location-related, mutually connected, and cascade-like reactions, thereby accelerating paces of tumor aggressiveness and metastasis. In this review, mechanisms underlying the distinct functional characterization of M1 and M2 macrophages are demonstrated to make sense of M1 and M2 as key regulators during cancer progression.
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M1 macrophages secrete CXCL9, CXCL10 and CXCL15 chemokines upon STAT1 signaling, which recruit cytotoxic T lymphocytes (CTLs) to the tumor.
“In addition, M1 macrophages secrete CXCL9, CXCL10 and CXCL15 chemokines upon STAT1 signaling, which recruit cytotoxic T lymphocytes (CTLs) to the tumor (43).”
From mRNA vaccine with unmodified uridine induces robust type I interferon-dependent anti-tumor immunity in a melanoma model (2022) · cites this paper as [43]
The Introduction’s “Major functional properties of M1 phenotype” section says M1 macrophages can strengthen CD8+ T-cell cytotoxic functions through IL-6, IL-12 and TNF. It does not say they secrete CXCL9, CXCL10 or CXCL15 upon STAT1 signaling, or that those chemokines recruit CTLs to tumors; searches for the chemokines and STAT1 found no supporting passage. (LLM, conf=0.88)
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2 retracted
Su, Z., Zhang, P., Yu, Y., Lu, H., Liu, Y., Ni, P., Su, X., Wang, D., Liu, Y., Wang, J., et al. (2016) · Scientific Reports · doi:10.1038/srep21884 · Cited by 82 · see citing works
RetractedLi, G., Guo, Z.-Z., Ma, X., Cao, N., Geng, S.-N., Zheng, Y.-Q., Meng, M.-J., Lin, H.-H., Han, G., & Du, G.-J. (2016) · Developmental and Comparative Immunology · doi:10.1016/j.dci.2016.01.010 · Cited by 25 · see citing works
RetractedHallmarks of Cancer: The Next Generation
Hanahan, D., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.02.013 · Cited by 66,590 · see citing works
Macrophage activation and polarization: nomenclature and experimental guidelines
Murray, P. J., Allen, J. E., Biswas, S. K., Fisher, E. A., Gilroy, D. W., Goerdt, S., Gordon, S., Hamilton, J. A., Ivashkiv, L. B., Lawrence, T., et al. (2014) · Immunity · doi:10.1016/j.immuni.2014.06.008 · Cited by 6,337 · see citing works
Macrophage Diversity Enhances Tumor Progression and Metastasis
Qian, B., & Pollard, J. W. (2010) · Cell · doi:10.1016/j.cell.2010.03.014 · Cited by 5,178 · see citing works
Functional Polarization of Tumour-Associated Macrophages by Tumour-Derived Lactic Acid
Colegio, O. R., Chu, N.-Q., Szabo, A. L., Chu, T., Rhebergen, A. M., Jairam, V., Cyrus, N., Brokowski, C. E., Eisenbarth, S. C., Phillips, G. M., et al. (2014) · Nature · doi:10.1038/nature13490 · Cited by 3,046 · see citing works
Tissue-resident macrophages originate from yolk-sac-derived erythro-myeloid progenitors
Gomez Perdiguero, E., Klapproth, K., Schulz, C., Busch, K., Azzoni, E., Crozet, L., Garner, H., Trouillet, C., de Bruijn, M. F., Geissmann, F., et al. (2015) · Nature · doi:10.1038/nature13989 · Cited by 2,339 · cited 1× · see citing works
“Differentiation and phenotypes of macrophages In normal tissues, macrophages could be differentiated into microglial cells in the brain, Kupffer cells in the liver, and Langerhans cells in the skin [14, 15].”
BackgroundFrom Monocytes to M1/M2 Macrophages: Phenotypical vs. Functional Differentiation
Italiani, P., & Boraschi, D. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00514 · Cited by 2,067 · see citing works
Llosa, N. J., Cruise, M., Tam, A., Wicks, E. C., Hechenbleikner, E. M., Taube, J. M., Blosser, R. L., Fan, H., Wang, H., Luber, B. S., et al. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-0863 · Cited by 1,487 · see citing works
Macrophages, innate immunity and cancer: balance, tolerance, and diversity
Mantovani, A., & Sica, A. (2010) · Current Opinion in Immunology · doi:10.1016/j.coi.2010.01.009 · Cited by 1,484 · see citing works
Macrophages and Therapeutic Resistance in Cancer
Ruffell, B., & Coussens, L. M. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.02.015 · Cited by 1,474 · see citing works
Ries, C. H., Cannarile, M. A., Hoves, S., Benz, J., Wartha, K., Runza, V., Rey-Giraud, F., Pradel, L. P., Feuerhake, F., Klaman, I., et al. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.05.016 · Cited by 1,384 · see citing works
Colony-stimulating factors in inflammation and autoimmunity
Hamilton, J. A. (2008) · Nature reviews. Immunology · doi:10.1038/nri2356 · Cited by 1,305 · see citing works
Tumors as Organs: Complex Tissues that Interface with the Entire Organism
Egeblad, M., Nakasone, E. S., & Werb, Z. (2010) · Developmental Cell · doi:10.1016/j.devcel.2010.05.012 · Cited by 1,230 · see citing works
Microglia in the adult brain arise from Ly-6ChiCCR2+ monocytes only under defined host conditions
Mildner, A., Schmidt, H., Nitsche, M., Merkler, D., Hanisch, U.-K., Mack, M., Heikenwalder, M., Brück, W., Priller, J., & Prinz, M. (2007) · Nature Neuroscience · doi:10.1038/nn2015 · Cited by 1,089 · see citing works
Wang, Y., Szretter, K. J., Vermi, W., Gilfillan, S., Rossini, C., Cella, M., Barrow, A. D., Diamond, M. S., & Colonna, M. (2012) · Nature Immunology · doi:10.1038/ni.2360 · Cited by 1,011 · see citing works
Ruffell, B., Chang-Strachan, D., Chan, V., Rosenbusch, A., Ho, C. M. T., Pryer, N., Daniel, D., Hwang, E. S., Rugo, H. S., & Coussens, L. M. (2014) · Cancer Cell · doi:10.1016/j.ccell.2014.09.006 · Cited by 1,008 · see citing works
New signals from the invasive front
Christofori, G. (2006) · Nature · doi:10.1038/nature04872 · Cited by 990 · see citing works
The role of macrophage phenotype in vascularization of tissue engineering scaffolds
Spiller, K. L., Anfang, R. R., Spiller, K. J., Ng, J., Nakazawa, K. R., Daulton, J. W., & Vunjak-Novakovic, G. (2014) · Biomaterials · doi:10.1016/j.biomaterials.2014.02.012 · Cited by 948 · see citing works
Zhou, D., Huang, C., Lin, Z., Zhan, S., Kong, L., Fang, C., & Li, J. (2014) · Cellular Signalling · doi:10.1016/j.cellsig.2013.11.004 · Cited by 778 · see citing works
Collagen as a double-edged sword in tumor progression
Fang, M., Yuan, J., Peng, C., & Li, Y. (2014) · Tumor Biology · doi:10.1007/s13277-013-1511-7 · Cited by 580 · see citing works
High Macrophage Infiltration along the Tumor Front Correlates with Improved Survival in Colon Cancer
Forssell, J., Öberg, Å., Henriksson, M. L., Stenling, R., Jung, A., & Palmqvist, R. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-2073 · Cited by 565 · see citing works
Clinical significance of macrophage heterogeneity in human malignant tumors
Komohara, Y., Jinushi, M., & Takeya, M. (2013) · Cancer Science · doi:10.1111/cas.12314 · Cited by 549 · see citing works
Beyond stem cells: self-renewal of differentiated macrophages
Sieweke, M. H., & Allen, J. E. (2013) · Science · doi:10.1126/science.1242974 · Cited by 503 · see citing works
A breast cancer stem cell niche supported by juxtacrine signalling from monocytes and macrophages
Lu, H., Clauser, K. R., Tam, W. L., Fröse, J., Ye, X., Eaton, E. N., Reinhardt, F., Donnenberg, V. S., Bhargava, R., Carr, S. A., et al. (2014) · Nature Cell Biology · doi:10.1038/ncb3041 · Cited by 457 · see citing works
M1 and M2 Macrophages: The Chicken and the Egg of Immunity
Mills, C. D., & Ley, K. F. (2014) · Journal of Innate Immunity · doi:10.1159/000364945 · Cited by 401 · see citing works
Tumor macrophages are pivotal constructors of tumor collagenous matrix
Afik, R., Zigmond, E., Vugman, M., Klepfish, M., Shimshoni, E., Pasmanik‐Chor, M., Shenoy, A., Bassat, E., Halpern, Z., Geiger, T., et al. (2016) · The Journal of Experimental Medicine · doi:10.1084/jem.20151193 · Cited by 376 · see citing works
Macrophages: Supportive cells for tissue repair and regeneration
Chazaud, B. (2013) · Immunobiology · doi:10.1016/j.imbio.2013.09.001 · Cited by 309 · see citing works
The immune system and cancer evasion strategies: therapeutic concepts
Muenst, S., Läubli, H., Soysal, S. D., Zippelius, A., Tzankov, A., & Hoeller, S. (2016) · Journal of Internal Medicine · doi:10.1111/joim.12470 · Cited by 304 · see citing works
Critical role of Trib1 in differentiation of tissue-resident M2-like macrophages
Satoh, T., Kidoya, H., Naito, H., Yamamoto, M., Takemura, N., Nakagawa, K., Yoshioka, Y., Morii, E., Takakura, N., Takeuchi, O., et al. (2013) · Nature · doi:10.1038/nature11930 · Cited by 300 · see citing works
Cohen, N., Shani, O., Raz, Y., Sharon, Y., Hoffman, D., Abramovitz, L., & Erez, N. (2017) · Oncogene · doi:10.1038/onc.2017.65 · Cited by 292 · see citing works
Raggi, F., Pelassa, S., Pierobon, D., Penco, F., Gattorno, M., Novelli, F., Eva, A., Varesio, L., Giovarelli, M., & Bosco, M. C. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01097 · Cited by 282 · see citing works
The Multifaceted Role of Perivascular Macrophages in Tumors
Lewis, C. E., Harney, A. S., & Pollard, J. W. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.05.017 · Cited by 248 · see citing works
Chemokines direct endothelial progenitors into tumor neovessels
Spring, H., Schüler, T., Arnold, B., Hämmerling, G. J., & Ganß, R. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0507158102 · Cited by 242 · see citing works
Macrophage Polarization and Bone Formation: A review
Horwood, N. J. (2015) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-015-8519-2 · Cited by 236 · see citing works
Tiainen, S., Tumelius, R., Rilla, K. J., Hämäläinen, K. M., Tammi, M., Tammi, R., Kosma, V., Oikari, S., & Auvinen, P. (2014) · Histopathology · doi:10.1111/his.12607 · Cited by 234 · see citing works
Burugu, S., Asleh, K., & Nielsen, T. O. (2016) · Breast Cancer · doi:10.1007/s12282-016-0698-z · Cited by 224 · see citing works
Therapeutic targeting of tumor suppressor genes
Morris, L. G. T., & Chan, T. A.-T. (2014) · Cancer · doi:10.1002/cncr.29140 · Cited by 201 · see citing works
Lim, S. Y., Yuzhalin, A. E., Gordon-Weeks, A. N., & Muschel, R. J. (2016) · Oncogene · doi:10.1038/onc.2016.107 · Cited by 174 · see citing works
Yang, C., Chen, W., Wang, S., Shi, D., Zhang, C., Lin, X., Dou, R., & Xiong, B. (2019) · International Journal of Biological Sciences · doi:10.7150/ijbs.29836 · Cited by 146 · see citing works
Tumour-infiltrating lymphocytes and the emerging role of immunotherapy in breast cancer
Luen, S. J., Savas, P. S., Fox, S. B., Salgado, R., & Loi, S. (2017) · Pathology · doi:10.1016/j.pathol.2016.10.010 · Cited by 137 · see citing works
Eguchi, J., Kong, X., Tenta, M., Wang, X., Kang, S., & Rosen, E. D. (2013) · Diabetes · doi:10.2337/db12-1327 · Cited by 129 · see citing works
Milky spots: omental functional units and hotbeds for peritoneal cancer metastasis
Liu, J., Geng, X.-F., & Li, Y. (2016) · Tumor Biology · doi:10.1007/s13277-016-4887-3 · Cited by 110 · see citing works
Self-citationPark, J. Y., Sung, J., Lee, J.-H., Park, Y.-K., Kim, Y. W., Kim, G. Y., Won, K. Y., & Lim, S. (2015) · Clinics and Research in Hepatology and Gastroenterology · doi:10.1016/j.clinre.2015.09.005 · Cited by 106 · see citing works
Macrophages: Gatekeepers of Tissue Integrity
Lavin, Y., & Mérad, M. (2013) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-13-0117 · Cited by 98 · see citing works
Dungan, L. S., McGuinness, N., Boon, L., Lynch, M. A., & Mills, K. H. G. (2014) · European Journal of Immunology · doi:10.1002/eji.201444612 · Cited by 88 · see citing works
Butoi, E. D., Gan, A., Tucureanu, M. M., Stan, D. L., Macarie, R. D., Constantinescu, C., Călin, M., Simionescu, M., & Mânduțeanu, I. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2016.04.001 · Cited by 80 · see citing works
Osinsky, S., Bubnovskaya, L., Ganusevich, І. І., et al. (2011) · Clinical & Translational Oncology · doi:10.1007/s12094-011-0630-0 · Cited by 73 · see citing works
Potas, J. R., Haque, F., Maclean, F. L., & Nisbet, D. R. (2015) · Journal of Immunological Methods · doi:10.1016/j.jim.2015.03.013 · Cited by 72 · see citing works
Gao, L., Wang, F.-Q., Li, H.-M., Yang, J., Ren, J.-G., He, K.-F., Liu, B., Zhang, W., & Zhao, Y.-F. (2016) · OncoTarget · doi:10.18632/oncotarget.13523 · Cited by 71 · see citing works
Promising landscape for regulating macrophage polarization: epigenetic viewpoint
Zhou, D., Yang, K., Chen, L., Zhang, W., Xu, Z., Zuo, J., Jiang, H., & Luan, J. (2017) · Oncotarget · doi:10.18632/oncotarget.17027 · Cited by 62 · see citing works
Feriotti, C., Loures, F. V., de Araújo, E. F., da Costa, T. A., & Calich, V. L. G. (2013) · PLoS ONE · doi:10.1371/journal.pone.0054845 · Cited by 49 · see citing works
Liu, X., Kiefl, R., Roskopf, C. C., Tian, F., & Huber, R. M. (2016) · PLoS ONE · doi:10.1371/journal.pone.0156268 · Cited by 47 · see citing works
da Silva, Z. E. V., Lehr, H., & Velin, D. (2014) · Pathobiology (Basel) · doi:10.1159/000357306 · Cited by 44 · see citing works
Distribution pattern of tumor associated macrophages predicts the prognosis of gastric cancer
Liu, J.-Y., Peng, C., Yang, G., Hu, W., Yang, X., Huang, C., Xiong, B., & Li, Y. (2017) · Oncotarget · doi:10.18632/oncotarget.21575 · Cited by 39 · see citing works
Self-citationPeng, C., Liu, J., Yang, G., & Li, Y. (2017) · International Journal of Nanomedicine · doi:10.2147/ijn.s143871 · Cited by 31 · see citing works
Self-citationHu, W., Fang, M., Zhao, H., Yan, S.-G., Yuan, J., Peng, C., Yang, G., Li, Y., & Li, J. (2014) · Biomaterials · doi:10.1016/j.biomaterials.2014.01.059 · Cited by 20 · see citing works
Ho, V. W., Hofs, E., Elisia, I., Lam, V., Hsu, B. E., Lai, J., Luk, B., Samudio, I. J., & Krystal, G. (2016) · PLoS ONE · doi:10.1371/journal.pone.0168072 · Cited by 19 · see citing works
Liu, J. Y., Yang, X. J., Geng, X.-F., Huang, C. Q., Yu, Y., & Li, Y. (2016) · PubMed · Cited by 13 · see citing works
Self-citationShi, X., Tang, Y., Sun, X., Liu, Y., Sun, Y. H., Sun, M., Jiang, Y., & Li, Y. (2016) · Molecular Medicine Reports · doi:10.3892/mmr.2016.5844 · Cited by 6 · see citing works
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Reschke, R., & Olson, D. (2022) · Cancers · doi:10.3390/cancers14102458 · Cited by 28 · see citing works
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- Authors
- Liu, J., Geng, X., Hou, J., & Wu, G.
- Affiliations
- Zhongnan Hospital of Wuhan University (CN)
- Corresponding author
- Hou, Jinxuan
- Wu, Gaosong
- Venue
- Cancer Cell International
- Published
- 2021-07-21
- Volume
- 21
- Issue
- 1
- Pages
- 389-389
- ISSN
- 1475-2867 (ISSN-L)
- PMC
- PMC8296555
- OpenAlex
- W3183953302
- Cited by
- 501
- References
- 60
- Citations by year
- 2026: 69 · 2025: 130 · 2024: 119 · 2023: 117 · 2022: 59 · 2021: 7
- FWCI
- 7.91
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Cancer Cell International (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Construction of Advantage Disciplines in Zhongnan Hospital of Wuhan University (XKJS202015)
- Improving the Ability of Diagnosis and Treatment of Difficult Diseases (Oncology) Registered Clinical Project of Zhongnan Hospital of Wuhan University (ZLYNXM202014)
- Fundamental Research Funds for Central Universities of the Central South University (2042019kf0141)
- Zhongnan Hospital of Wuhan University Science, Technology and Innovation Seed Fund (WJ2019H015)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Psychiatry and Mental health › Cancer, Stress, Anesthesia, and Immune Response
- Keywords
- M1 macrophages, M2 macrophages, tumor-associated macrophages, macrophage polarization, tumor progression, tumor microenvironment, immunosuppression, angiogenesis, metastasis, stromal remodeling, phagocytosis
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