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Macrophage Polarization in the Tumor Microenvironment: Modulation and Mimicry

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Handbook of Cancer and Immunology

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Abstract

Macrophages are innate immune cells that dominate the tumor microenvironment. Environmental cues polarize tumor-associated macrophages (TAMs) into phenotypically and functionally divergent populations that are regarded as anti-tumorigenic (M1) or pro-tumorigenic (M2). It is becoming increasingly evident that the process of polarization incorporates a range of alterations that rather reflects a phenotypic continuum that is mutable. TAMs both manipulate and can be manipulated by tumor cells to ensure tumor progression. In this chapter, we consider the role of TAMS in the tumor microenvironment, and the factors that drive their spatial, phenotypic, and functional changes. Lastly, we consider immunotherapeutic options that would permit targeting macrophage polarity as a strategy to prevent tumor progression.

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References

  • Albina JE, Mastrofrancesco B (1993) Modulation of glucose metabolism in macrophages by products of nitric oxide synthase. Am J Phys 264:C1594–C1599

    Article  CAS  Google Scholar 

  • Almatroodi SA, McDonald CF, Darby IA et al (2016) Characterization of M1/M2 tumour-associated macrophages (TAMs) and Th1/Th2 cytokine profiles in patients with NSCLC. Cancer Microenviron 9:1–11

    Article  CAS  Google Scholar 

  • Amici SA, Dong J, Guerau-de-Arellano M (2017) Molecular mechanisms modulating the phenotype of macrophages and microglia. Front Immunol 8:1–18

    Article  Google Scholar 

  • Arranz A, Doxaki C, Vergadi E et al (2012) Akt1 and Akt2 protein kinases differentially contribute to macrophage polarization. Proc Natl Acad Sci U S A 109:9517–9522

    Article  CAS  Google Scholar 

  • Batlle E, Massagué J (2019) Transforming growth factor-β signaling in immunity and cancer. Immunity 50:924–940

    Article  CAS  Google Scholar 

  • Bertani FR, Mozetic P, Fioramonti M et al (2017) Classification of M1/M2-polarized human macrophages by label-free hyperspectral reflectance confocal microscopy and multivariate analysis. Sci Rep 7:8965

    Article  Google Scholar 

  • Bianchini F, Massi D, Marconi C et al (2007) Expression of cyclo-oxygenase-2 in macrophages associated with cutaneous melanoma at different stages of progression. Prostaglandins Other Lipid Mediat 83:320–328

    Article  CAS  Google Scholar 

  • Biswas SK, Lewis CE (2010) NF-κB as a central regulator of macrophage function in tumors. J Leukoc Biol 88:877–884

    Article  CAS  Google Scholar 

  • Cavnar MJ, Turcotte S, Katz SC et al (2017) Tumor-associated macrophage infiltration in colorectal cancer liver metastases is associated with better outcome. Ann Surg Oncol 24:1835–1842

    Article  Google Scholar 

  • Chen X, Liu Y, Gao Y et al (2021) The roles of macrophage polarization in the host immune response to sepsis. Int Immunopharmacol 96:107791

    Article  CAS  Google Scholar 

  • Chittezhath M, Dhillon MK, Lim JY et al (2014) Molecular profiling reveals a tumor-promoting phenotype of monocytes and macrophages in human cancer progression. Immunity 41:815–829

    Article  CAS  Google Scholar 

  • Cui YL, Li HK, Zhou HY et al (2013) Correlations of tumor-associated macrophage subtypes with liver metastases of colorectal cancer. Asian Pacific J Cancer Prev 14:1003–1007

    Article  Google Scholar 

  • De Rosa V, Di Rella F, Di Giacomo A, Matarese G (2017) Regulatory T cells as suppressors of anti-tumor immunity: role of metabolism. Cytokine Growth Factor Rev 35:15–25

    Article  Google Scholar 

  • Dubey P, Shrivastava R, Tripathi C et al (2014) Cyclooxygenase-2 inhibition attenuates hypoxic cancer cells induced M2-polarization of macrophages. Cell Mol Biol 60:10–15

    CAS  Google Scholar 

  • El Kasmi KC, Stenmark KR (2015) Contribution of metabolic reprogramming to macrophage plasticity and function. Semin Immunol 27:267–275

    Article  Google Scholar 

  • Esbona K, Inman D, Saha S et al (2016) COX-2 modulates mammary tumor progression in response to collagen density. Breast Cancer Res 18:35

    Article  Google Scholar 

  • Fortin CF, Cloutier A, Ear T et al (2011) A class IA PI3K controls inflammatory cytokine production in human neutrophils. Eur J Immunol 41:1709–1719

    Article  CAS  Google Scholar 

  • Fouad YA, Aanei C (2017) Revisiting the hallmarks of cancer. Am J Cancer Res 7:1016–1036

    CAS  Google Scholar 

  • Galván-Peña S, O’Neill LAJ (2014) Metabolic reprogramming in macrophage polarization. Front Immunol 5:1–6

    Google Scholar 

  • Germano G, Frapolli R, Belgiovine C et al (2013) Role of macrophage targeting in the antitumor activity of trabectedin. Cancer Cell 23:249–262

    Article  CAS  Google Scholar 

  • Gong D, Shi W, Yi S et al (2012) TGFβ signaling plays a critical role in promoting alternative macrophage activation. BMC Immunol 13:31

    Article  CAS  Google Scholar 

  • Gordon S, Plüddemann A (2019) The mononuclear phagocytic system generation of diversity. Front Immunol 10:1–10

    Article  CAS  Google Scholar 

  • Goswami KK, Ghosh T, Ghosh S et al (2017) Tumor promoting role of anti-tumor macrophages in tumor microenvironment. Cell Immunol 316:1–10

    Article  CAS  Google Scholar 

  • Guiducci C, Vicari AP, Sangaletti S (2005) Redirecting in vivo elicited tumor infiltrating macrophages and dendritic cells towards tumor rejection. Cancer Res 65:3437–3446

    Article  CAS  Google Scholar 

  • Guo Z, Song J, Hao J et al (2019) M2 macrophages promote NSCLC metastasis by upregulating CRYAB. Cell Death Dis 10:377

    Article  Google Scholar 

  • Han X, Ma W, Zhu Y et al (2020) Advanced glycation end products enhance macrophage polarization to the M1 phenotype via the HIF-1α/PDK4 pathway. Mol Cell Endocrinol 514:110878

    Article  CAS  Google Scholar 

  • Hensler M, Kasikova L, Fiser K et al (2020) M2-like macrophages dictate clinically relevant immunosuppression in metastatic ovarian cancer. J Immunother Cancer 8:1–12

    Article  Google Scholar 

  • Hong S, Lim S, Li AG et al (2007) Smad7 binds to the adaptors TAB2 and TAB3 to block recruitment of the kinase TAK1 to the adaptor TRAF2. Nat Immunol 8:504–513

    Article  CAS  Google Scholar 

  • Honkanen TJ, Tikkanen A, Karihtala P et al (2019) Prognostic and predictive role of tumour-associated macrophages in HER2 positive breast cancer. Sci Rep 9:1–9

    Article  CAS  Google Scholar 

  • Hörber S, Hildebrand DG, Lieb WS et al (2016) The atypical inhibitor of NF-κB, IκBζ, controls macrophage interleukin-10 expression. J Biol Chem 291:12851–12961

    Article  Google Scholar 

  • Hu JM, Liu K, Liu JH et al (2017) CD163 as a marker of M2 macrophage, contribute to predicte aggressiveness and prognosis of Kazakh esophageal squamous cell carcinoma. Oncotarget 8:21526–21538

    Article  Google Scholar 

  • Ishizu T, Eichin D, Padzik A et al (2021) Head and neck squamous cell carcinoma cell lines have an immunomodulatory effect on macrophages independent of hypoxia and toll-like receptor 9. BMC Cancer 21:1–13

    Article  Google Scholar 

  • Torres-Castro I, Arroyo-Camarena ÚD, Martínez-Reyes CP, Gómez-Arauz AY, Dueñas-Andrade Y, Hernández-Ruiz J, Béjar YL, Zaga-Clavellina V, Morales-Montor J, Terrazas LI, Kzhyshkowska J, Escobedo G (2016) Human monocytes and macrophages undergo M1-type inflammatory polarization in response to high levels of glucose. Immunology Letters 17681–89 S0165247816301031 10.1016/j.imlet.2016.06.001

    Google Scholar 

  • Jablonski KA, Amici SA, Webb LM et al (2015) Novel markers to delineate murine M1 and M2 macrophages. PLoS One 10(12):e0145342

    Article  Google Scholar 

  • Jaguin M, Houlbert N, Fardel O, Lecureur V (2013) Polarization profiles of human M-CSF-generated macrophages and comparison of M1-markers in classically activated macrophages from GM-CSF and M-CSF origin. Cell Immunol 281:51–61

    Article  CAS  Google Scholar 

  • Jamiyan T, Kuroda H, Yamaguchi R et al (2020) CD68- and CD163-positive tumor-associated macrophages in triple negative cancer of the breast. Virchows Arch 477:767–775

    Article  CAS  Google Scholar 

  • Jayasingam SD, Citartan M, Thang TH et al (2020) Evaluating the polarization of tumor-associated macrophages into M1 and M2 phenotypes in human cancer tissue: technicalities and challenges in routine clinical practice. Front Oncol 9:1512

    Article  Google Scholar 

  • Jiang N, Dai Q, Su X et al (2020) Role of PI3K/AKT pathway in cancer: the framework of malignant behavior. Mol Biol Rep 47:4587–4629

    Article  CAS  Google Scholar 

  • Josephs DH, Bax HJ, Karagiannis SN (2015) Tumour-associated macrophage polarisation and re-education with immunotherapy. Front Biosci (Elite Ed) 7:293–308

    Google Scholar 

  • Khorana AA, Ryan CK, Cox C et al (2003) Vascular endothelial growth factor, CD68, and epidermal growth factor receptor expression and survival in patients with stage II and stage III colon carcinoma: a role for the host response in prognosis. Cancer 97:960–968

    Article  Google Scholar 

  • Kim Y, Wen X, Bae JM et al (2018) The distribution of intratumoral macrophages correlates with molecular phenotypes and impacts prognosis in colorectal carcinoma. Histopathology 73:663–671

    Article  Google Scholar 

  • Koide N, Sugiyama T, Mori I et al (2003) C2-ceramide inhibits LPS-induced nitric oxide production in RAW 264.7 macrophage cells through down-regulating the activation of Akt. J Endotoxin Res 9:85–90

    CAS  Google Scholar 

  • Krishnan V, Schaar B, Tallapragada S, Dorigo O (2018) Tumor associated macrophages in gynecologic cancers. Gynecol Oncol 149:205–213

    Article  CAS  Google Scholar 

  • Kudlik G, Hegyi B, Czibula Á et al (2016) Mesenchymal stem cells promote macrophage polarization toward M2b-like cells. Exp Cell Res 348:36–45

    Article  CAS  Google Scholar 

  • Larionova I, Tuguzbaeva G, Ponomaryova A et al (2020) Tumor-associated macrophages in human breast, colorectal, lung, ovarian and prostate cancers. Front Oncol 10:1–34

    Article  Google Scholar 

  • Leão FB, Vaughn LS, Bhatt D et al (2020) Toll-like receptor (TLR)-induced Rasgef1b expression in macrophages is regulated by NF-κB through its proximal promoter. Int J Biochem Cell Biol 127:105840

    Article  Google Scholar 

  • Li H, Yang B, Huang J et al (2015) Cyclooxygenase-2 in tumor-associated macrophages promotes breast cancer cell survival by triggering a positive-feedback loop between macrophages and cancer cells. Oncotarget 6:29637–29650

    Article  Google Scholar 

  • Lin CN, Wang CJ, Chao YJ et al (2015) The significance of the co-existence of osteopontin and tumor-associated macrophages in gastric cancer progression. BMC Cancer 15:1–10

    Article  Google Scholar 

  • Lin Y, Xu J, Lan H (2019) Tumor-associated macrophages in tumor metastasis: biological roles and clinical therapeutic applications. J Hematol Oncol 12:1–16

    Article  Google Scholar 

  • Liu Y, Stewart KN, Bishop E et al (2008) Unique expression of suppressor of cytokine signaling 3 is essential for classical macrophage activation in rodents in vitro and in vivo. J Immunol 180:6270–6278

    Article  CAS  Google Scholar 

  • Liu Z, Li Y, Zhao W et al (2011) Demonstration of vasculogenic mimicry in astrocytomas and effects of Endostar on U251 cells. Pathol Res Pract 207:645–651

    Article  CAS  Google Scholar 

  • Liu R, Yang K, Meng C et al (2012) Vasculogenic mimicry is a marker of poor prognosis in prostate cancer. Cancer Biol Ther 13:527–533

    Article  CAS  Google Scholar 

  • Liu CY, Xu JY, Shi XY et al (2013) M2-polarized tumor-associated macrophages promoted epithelial-mesenchymal transition in pancreatic cancer cells, partially through TLR4/IL-10 signaling pathway. Lab Investig 93:844–854

    Article  CAS  Google Scholar 

  • Liu B, Qu L, Yan S (2015) Cyclooxygenase-2 promotes tumor growth and suppresses tumor immunity. Cancer Cell Int 15:106

    Article  Google Scholar 

  • Liu X, Lv Z, Zhou S et al (2021) MTDH in macrophages promotes the vasculogenic mimicry via VEGFA-165/Flt-1 signaling pathway in head and neck squamous cell carcinoma. Int Immunopharmacol 96:107776

    Article  CAS  Google Scholar 

  • Luo Y (2006) Targeting tumor-associated macrophages as a novel strategy against breast cancer. J Clin Investig 116:2132–2141

    Article  CAS  Google Scholar 

  • Lurier EB, Dalton D, Dampier W et al (2017) Transcriptome analysis of IL-10-stimulated (M2c) macrophages by next-generation sequencing. Immunobiology 222:847–856

    Article  CAS  Google Scholar 

  • Mackaness G (1962) Cellular resistance to infection. J Exp Med 116:381–406

    Article  CAS  Google Scholar 

  • Malyshev I, Malyshev Y (2015) Current concept and update of the macrophage plasticity concept: intracellular mechanisms of reprogramming and M3 macrophage “switch” phenotype. Biomed Res Int 2015:341308

    Article  Google Scholar 

  • Mantovani A, Sozzani S, Locati M et al (2002) Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol 23:549–555

    Article  CAS  Google Scholar 

  • Mantovani A, Sica A, Locati M (2005) Macrophage polarization comes of age. Immunity 23:344–346

    Article  CAS  Google Scholar 

  • Martinez FO, Gordon S (2014) The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep 6:13

    Article  Google Scholar 

  • Martinez FO, Gordon S, Locati M, Mantovani A (2006) Transcriptional profiling of the human monocyte-to-macrophage differentiation and polarization: new molecules and patterns of gene expression. J Immunol 177:7303–7311

    Article  CAS  Google Scholar 

  • Martinez FO, Sica A, Mantovani A, Locati M (2008) Macrophage activation and polarization. Front Biosci 13:453–461

    Article  CAS  Google Scholar 

  • Miller YI, Viriyakosol S, Worrall DS et al (2005) Toll-like receptor 4-dependent and -independent cytokine secretion induced by minimally oxidized low-density lipoprotein in macrophages. Arterioscler Thromb Vasc Biol 25:1213–1219

    Article  CAS  Google Scholar 

  • Mills CD, Kincaid K, Alt JM et al (2000) M-1/M-2 macrophages and the Th1/Th2 paradigm. J Immunol 164:6166–6173

    Article  CAS  Google Scholar 

  • Mitchem JB, Brennan DJ, Knolhoff BL (2013) Targeting tumor-infiltrating macrophages decreases tumor-initiating cells, relieves immunosuppression, and improves chemotherapeutic responses. Cancer Res 73:1128–1141

    Article  CAS  Google Scholar 

  • Morita Y, Zhang R, Leslie M et al (2017) Pathologic evaluation of tumor-associated macrophage density and vessel inflammation in invasive breast carcinomas. Oncol Lett 14:2111–2118

    Article  CAS  Google Scholar 

  • Mosmann TR, Coffman RL (1989) TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol 7:145–173

    Article  CAS  Google Scholar 

  • Mosmann TR, Cherwinski H, Bond MW et al (1986) Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 136:2348–2357

    CAS  Google Scholar 

  • Mosser DM, Edwards JP (2008) Exploring the full spectrum of macrophage activation. Nat Rev Immunol 8:958–969

    Article  CAS  Google Scholar 

  • Motta JM, Rumjanek VM, Mantovani A, Locati M (2021) Tumor-released products promote bone marrow-derived macrophage survival and proliferation. Biomedicine 9(10):1387

    CAS  Google Scholar 

  • Munir MT, Kay MK, Kang MH et al (2021) Tumor-associated macrophages as multifaceted regulators of breast tumor growth. Int J Mol Sci 22(12):6526

    Article  CAS  Google Scholar 

  • Murdoch C, Giannoudis A, Lewis CE (2004) Mechanisms regulating the recruitment of macrophages into hypoxic areas of tumors and other ischemic tissues. Blood 104:2224–2234

    Article  CAS  Google Scholar 

  • Murray PJ, Allen JE, Biswas SK et al (2014) Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity 41:14–20

    Article  CAS  Google Scholar 

  • Naiki Y, Michelsen KS, Zhang W et al (2005) Transforming growth factor-beta differentially inhibits MyD88-dependent, but not TRAM- and TRIF-dependent, lipopolysaccharide-induced TLR4 signaling. J Biol Chem 280:5491–5495

    Article  CAS  Google Scholar 

  • Nathan CF, Murray HW, Wlebe IE, Rubin BY (1983) Identification of interferon-γ, as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity. J Exp Med 158:670–689

    Article  CAS  Google Scholar 

  • Pantano F, Berti P, Guida FM et al (2013) The role of macrophages polarization in predicting prognosis of radically resected gastric cancer patients. J Cell Mol Med 17:1415–1421

    Article  CAS  Google Scholar 

  • Pellizzari G, Hoskin C, Crescioli S et al (2019) IgE re-programs alternatively-activated human macrophages towards pro-inflammatory anti-tumoural states. EBioMedicine 43:67–81

    Article  Google Scholar 

  • Petty AJ, Owen DH, Yang Y, Huang X (2021) Targeting tumor-associated macrophages in cancer immunotherapy. Cancers (Basel) 13:1–19

    Article  Google Scholar 

  • Pinto ML, Rios E, Durães C et al (2019) The two faces of tumor-associated macrophages and their clinical significance in colorectal cancer. Front Immunol 10:1–12

    Article  Google Scholar 

  • Polumuri SK, Toshchakov VY, Vogel SN (2007) Role of phosphatidylinositol-3 kinase in transcriptional regulation of TLR-induced IL-12 and IL-10 by Fc gamma receptor ligation in murine macrophages. J Immunol Baltim Md 1950 179:236–246

    CAS  Google Scholar 

  • Porta C, Rimoldi M, Raes G et al (2009) Tolerance and M2 (alternative) macrophage polarization are related processes orchestrated by p50 nuclear factor kappaB. Proc Natl Acad Sci U S A 106:14978–14983

    Article  CAS  Google Scholar 

  • Qin Y, Garrison BS, Ma W et al (2018) A milieu molecule for TGF-β required for microglia function in the nervous system. Cell 174:156–171.e16

    Article  CAS  Google Scholar 

  • Qiu SQ, Waaijer SJH, Zwager MC et al (2018) Tumor-associated macrophages in breast cancer: innocent bystander or important player? Cancer Treat Rev 70:178–189

    Article  CAS  Google Scholar 

  • Raggi F, Pelassa S, Pierobon D et al (2017) Regulation of human macrophage M1-M2 polarization balance by hypoxia and the triggering receptor expressed on myeloid cells-1. Front Immunol 8:1–18

    Article  Google Scholar 

  • Rakaee M, Busund LTR, Jamaly S et al (2019) Prognostic value of macrophage phenotypes in resectable non–small cell lung cancer assessed by multiplex immunohistochemistry. Neoplasia 21:282–293

    Article  CAS  Google Scholar 

  • Ramos RN, Rodriguez C, Hubert M et al (2020) CD163+ tumor-associated macrophage accumulation in breast cancer patients reflects both local differentiation signals and systemic skewing of monocytes. Clin Transl Immunol 9(2):e1108

    Article  Google Scholar 

  • Rath M, Müller I, Kropf P et al (2014) Metabolism via arginase or nitric oxide synthase: two competing arginine pathways in macrophages. Front Immunol 5:1–10

    Article  Google Scholar 

  • Restrepo CM, Llanes A, Herrera L et al (2021) Gene expression patterns associated with leishmania panamensis infection in macrophages from BALB/c and C57BL/6 mice. PLoS Negl Trop Dis 15:1–20

    Article  Google Scholar 

  • Rodríguez-Prados J-C, Través PG, Cuenca J et al (2010) Substrate fate in activated macrophages: a comparison between innate, classic, and alternative activation. J Immunol 185:605–614

    Article  Google Scholar 

  • Rong X, Huang B, Qiu S et al (2016) Tumor-associated macrophages induce vasculogenic mimicry of glioblastoma multiforme through cyclooxygenase-2 activation. Oncotarget 7:83976–83986

    Article  Google Scholar 

  • Sans-Fons MG, Yeramian A, Pereira-Lopes S et al (2013) Arginine transport is impaired in C57Bl/6 mouse macrophages as a result of a deletion in the promoter of Slc7a2 (CAT2), and susceptibility to Leishmania infection is reduced. J Infect Dis 207:1684–1693

    Article  CAS  Google Scholar 

  • Schmieder A, Michel J, Schönhaar K et al (2012) Differentiation and gene expression profile of tumor-associated macrophages. Semin Cancer Biol 22:289–297

    Article  CAS  Google Scholar 

  • Shigeoka M, Urakawa N, Nakamura T et al (2013) Tumor associated macrophage expressing CD204 is associated with tumor aggressiveness of esophageal squamous cell carcinoma. Cancer Sci 104:1112–1119

    Article  CAS  Google Scholar 

  • Sousa S, Brion R, Lintunen M et al (2015) Human breast cancer cells educate macrophages toward the M2 activation status. Breast Cancer Res 17:1–14

    Article  CAS  Google Scholar 

  • Stein BM, Keshav S, Harris N, Gordon S (1992) Interleukin 4 potently enhances murine macrophage mannose receptor activity. J Exp Med 176:287–292

    Article  CAS  Google Scholar 

  • Strassheim D, Asehnoune K, Park J-S et al (2004) Phosphoinositide 3-kinase and Akt occupy central roles in inflammatory responses of Toll-like receptor 2-stimulated neutrophils. J Immunol Baltim Md 1950(172):5727–5733

    Google Scholar 

  • Thomas AC, Mattila JT (2014) “Of mice and men”: arginine metabolism in macrophages. Front Immunol 5:1–7

    Article  CAS  Google Scholar 

  • Torroella-Kouri M, Silvera R, Rodriguez D et al (2009) Identification of a subpopulation of macrophages in mammary tumor-bearing mice that are neither M1 nor M2 and are less differentiated. Cancer Res 69:4800–4809

    Article  CAS  Google Scholar 

  • Totzke G, Essmann F, Pohlmann S et al (2006) A novel member of the IκB family, human IκB-ζ, inhibits transactivation of p65 and its DNA binding. J Biol Chem 281:12645–12654

    Article  CAS  Google Scholar 

  • Treps L, Faure S, Clere N (2021) Vasculogenic mimicry, a complex and devious process favoring tumorigenesis – interest in making it a therapeutic target. Pharmacol Ther 223:107805

    Article  CAS  Google Scholar 

  • Utsugi M, Dobashi K, Ono A et al (2009) PI3K p110beta positively regulates lipopolysaccharide-induced IL-12 production in human macrophages and dendritic cells and JNK1 plays a novel role. J Immunol Baltim Md 1950(182):5225–5231

    Google Scholar 

  • Van Dalen FJ, Van Stevendaal MHME, Fennemann FL et al (2019) Molecular repolarisation of tumour-associated macrophages. Molecules 24(1):9

    Article  Google Scholar 

  • Van Den Ham H, De Jager W, Bijlsma JWJ et al (2009) Differential cytokine profiles in juvenile idiopathic arthritis subtypes revealed by cluster analysis. Rheumatology 48:899–905

    Article  Google Scholar 

  • Vogel DYS, Glim JE, Stavenuiter AWD et al (2014) Human macrophage polarization in vitro: maturation and activation methods compared. Immunobiology 219:695–703

    Article  CAS  Google Scholar 

  • Wagenblast E, Soto M, Gutiérrez-Ángel S et al (2015) A model of breast cancer heterogeneity reveals vascular mimicry as a driver of metastasis. Nature 520:358–362

    Article  CAS  Google Scholar 

  • Wang N, Liang H, Zen K (2014) Molecular mechanisms that influence the macrophage M1-M2 polarization balance. Front Immunol 5:1–9

    Article  Google Scholar 

  • Wang L, Li YS, Yu LG et al (2020a) Galectin-3 expression and secretion by tumor-associated macrophages in hypoxia promotes breast cancer progression. Biochem Pharmacol 178:114113

    Article  CAS  Google Scholar 

  • Wang X, Peng H, Huang Y et al (2020b) Post-translational modifications of IκBα: the state of the art. Front Cell Dev Biol 8:1–15

    Google Scholar 

  • Wang Y, Lyu Z, Qin Y et al (2020c) FOXO1 promotes tumor progression by increased M2 macrophage infiltration in esophageal squamous cell carcinoma. Theranostics 10:11535–11548

    Article  CAS  Google Scholar 

  • Whyte CS, Bishop ET, Rückerl D et al (2011) Suppressor of cytokine signaling (SOCS)1 is a key determinant of differential macrophage activation and function. J Leukoc Biol 90:845–854

    Article  CAS  Google Scholar 

  • Xie S, Chen M, Yan B et al (2014) Identification of a role for the PI3K/AKT/mTOR signaling pathway in innate immune cells. PLoS One 9:e94496

    Article  Google Scholar 

  • Yang M, Li Z, Ren M et al (2018) Stromal infiltration of tumor-associated macrophages conferring poor prognosis of patients with basal-like breast carcinoma. J Cancer 9:2308–2316

    Article  Google Scholar 

  • Yang C, Wei C, Wang S et al (2019a) Elevated CD163+/CD68+ ratio at tumor invasive front is closely associated with aggressive phenotype and poor prognosis in colorectal cancer. Int J Biol Sci 15:984–998

    Article  CAS  Google Scholar 

  • Yang J, Nie J, Ma X et al (2019b) Targeting PI3K in cancer: mechanisms and advances in clinical trials. Mol Cancer 18:26

    Article  Google Scholar 

  • Yin S, Huang J, Li Z et al (2017) The prognostic and clinicopathological significance of tumor-associated macrophages in patients with gastric cancer: a meta-analysis. PLoS One 12:1–14

    Google Scholar 

  • Yin M, Shen J, Yu S et al (2019) Tumor-associated macrophages (Tams): a critical activator in ovarian cancer metastasis. Onco Targets Ther 12:8687–8699

    Article  CAS  Google Scholar 

  • Yu LX, Yan L, Yang W et al (2014) Platelets promote tumour metastasis via interaction between TLR4 and tumour cell-released high-mobility group box 1 protein. Nat Commun 5:5256

    Article  CAS  Google Scholar 

  • Yuan A, Hsiao YJ, Chen HY et al (2015) Opposite effects of M1 and M2 macrophage subtypes on lung cancer progression. Sci Rep 5:1–12

    Article  Google Scholar 

  • Zeisberger SM, Odermatt B, Marty C et al (2006) Clodronate-liposome-mediated depletion of tumour-associated macrophages: a new and highly effective antiangiogenic therapy approach. Br J Cancer 95:272–281

    Article  CAS  Google Scholar 

  • Zhang Y, Wang X, Yang H et al (2013) Kinase AKT controls innate immune cell development and function. Immunology 140:143–152

    Article  CAS  Google Scholar 

  • Zhang M, He Y, Sun X et al (2014) A high M1/M2 ratio of tumor-associated macrophages is associated with extended survival in ovarian cancer patients. J Ovarian Res 7:1–16

    Article  Google Scholar 

  • Zhang F, Wang H, Wang X et al (2016a) TGF-β induces M2-like macrophage polarization via SNAIL-mediated suppression of a pro-inflammatory phenotype. Oncotarget 7:52294–52306

    Article  Google Scholar 

  • Zhang J, Yan Y, Yang Y et al (2016b) High infiltration of tumor-associated macrophages influences poor prognosis in human gastric cancer patients, associates with the phenomenon of EMT. Medicine (Baltimore) 95:1–6

    Google Scholar 

  • Zhang C, Yang M, Ericsson AC (2021) Function of macrophages in disease: current understanding on molecular mechanisms. Front Immunol 12:1–12

    Google Scholar 

  • Zhao X, Qu J, Sun Y et al (2017) Prognostic significance of tumor-associated macrophages in breast cancer: a meta-analysis of the literature. Oncotarget 8:30576–30586

    Article  Google Scholar 

  • Zheng X, Turkowski K, Mora J et al (2017) Redirecting tumor-associated macrophages to become tumoricidal effectors as a novel strategy for cancer therapy. Oncotarget 8:48436–48452

    Article  Google Scholar 

  • Zinatizadeh MR, Schock B, Chalbatani GM et al (2021) The Nuclear Factor Kappa B (NF-kB) signaling in cancer development and immune diseases. Genes Dis 8:287–297

    Article  CAS  Google Scholar 

Download references

Acknowledgments

TNA acknowledges the National Research Foundation (M121263) for their support. Research reported in this publication was also supported by the South African Medical Research Council under a Self-Initiated Research Grant held by EEN and PNF.

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Authors and Affiliations

  1. School of Anatomical Sciences, Faculty of the Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

    Tanya N. Augustine

  2. Department of Surgery, School of Clinical Medicine, Faculty of the Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

    Ekene Emmanuel Nweke & Pascaline N. Fru

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  1. Tanya N. Augustine
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  2. Ekene Emmanuel Nweke
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  3. Pascaline N. Fru
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Correspondence to Tanya N. Augustine .

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  1. Division of Clinical Immunology, Karolinska University Hospital, Huddinge, Sweden

    Nima Rezaei

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Augustine, T.N., Nweke, E.E., Fru, P.N. (2022). Macrophage Polarization in the Tumor Microenvironment: Modulation and Mimicry. In: Rezaei, N. (eds) Handbook of Cancer and Immunology. Springer, Cham. https://doi.org/10.1007/978-3-030-80962-1_90-1

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  • DOI: https://doi.org/10.1007/978-3-030-80962-1_90-1

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-80962-1

  • Online ISBN: 978-3-030-80962-1

  • eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

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