Significance of polarization and targeted therapy of macrophages in tumor microenvironment_West China Medical Journal

Authors：

XIE Yuyu ,  DUAN Xinsuo

Department of Dermatology, Affiliated Hospital of Chengde Medical University, Chengde, Hebei 067000, P. R. China;

Corresponding author：

DUAN Xinsuo, Email: 15633142680@163.com

Keywords：

Tumor microenvironment; Polarization; Tumor-associated macrophages; Targeted therapy

DOI：

10.7507/1002-0179.202001027

Video：

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Abstract Full text Figures/Tables Video References Cited by

In the tumor microenvironment, tumor-associated macrophage, as polarized macrophages M2 phenotype, can promote tumor progression and affect the prognosis of cancer. Significant attention has been drawn towards tumor-associated macrophage in recent years. In this review, we describe the polarization state of macrophages determined by tumor microenvironment and the recruitment of tumor-associated macrophage. We also pay special attention to the interaction between tumor-associated macrophages and tumors, discuss and summarize various targeted therapy strategies for tumor-associated macrophages, aiming to provide a reference for the future development of these novel and effective anti-cancer treatments.

Citation： XIE Yuyu, DUAN Xinsuo. Significance of polarization and targeted therapy of macrophages in tumor microenvironment. West China Medical Journal, 2021, 36(5): 679-685. doi: 10.7507/1002-0179.202001027 Copy

1.	Roma-Rodrigues C, Mendes R, Baptista PV, et al. Targeting tumor microenvironment for cancer therapy. Int J Mol Sci, 2019, 20(4): 840.
2.	Morrison C. Immuno-oncologists eye up macrophage targets. Nat Rev Drug Discov, 2016, 15(6): 373-374.
3.	Long KB, Collier AI, Beatty GL. Macrophages: key orchestrators of a tumor microenvironment defined by therapeutic resistance. Mol Immunol, 2019, 110: 3-12.
4.	Dehne N, Mora J, Namgaladze D, et al. Cancer cell and macrophage cross-talk in the tumor microenvironment. Curr Opin Pharmacol, 2017, 35: 12-19.
5.	Ostuni R, Kratochvill F, Murray PJ, et al. Macrophages and cancer: from mechanisms to therapeutic implications. Trends Immunol, 2015, 36(4): 229-239.
6.	Jeannin P, Paolini L, Adam C, et al. The roles of CSFs on the functional polarization of tumor-associated macrophages. FEBS J, 2018, 285(4): 680-699.
7.	Salmaninejad A, Valilou SF, Soltani A, et al. Tumor-associated macrophages: role in cancer development and therapeutic implications. Cell Oncol (Dordr), 2019, 42(5): 591-608.
8.	Sica A, Schioppa T, Mantovani A, et al. Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression: potential targets of anti-cancer therapy. Eur J Cancer, 2006, 42(6): 717-727.
9.	Netea-Maier RT, Smit JWA, Netea MG. Metabolic changes in tumor cells and tumor-associated macrophages: a mutual relationship. Cancer Lett, 2018, 413: 102-109.
10.	Lewis CE, Pollard JW. Distinct role of macrophages in different tumor microenvironments. Cancer Res, 2006, 66(2): 605-612.
11.	Kielbassa K, Vegna S, Ramirez C, et al. Understanding the origin and diversity of macrophages to tailor their targeting in solid cancers. Front Immunol, 2019, 10: 2215.
12.	van Eeden SF, Tan WC, Suwa T, et al. Cytokines involved in the systemic inflammatory response induced by exposure to particulate matter air pollutants (PM10). Am J Respir Crit Care Med, 2001, 164(5): 826-830.
13.	Hamilton G, Rath B, Klameth L, et al. Small cell lung cancer: recruitment of macrophages by circulating tumor cells. Oncoimmunology, 2015, 5(3): e1093277.
14.	Kortlever RM, Sodir NM, Wilson CH, et al. Myc cooperates with ras by programming inflammation and immune suppression. Cell, 2017, 171(6): 1301-1315. e14.
15.	Krenkel O, Tacke F. Liver macrophages in tissue homeostasis and disease. Nat Rev Immunol, 2017, 17(5): 306-321.
16.	Yu LX, Ling Y, Wang HY. Role of nonresolving inflammation in hepatocellular carcinoma development and progression. NPJ Precis Oncol, 2018, 2(1): 6.
17.	Dixon LJ, Barnes M, Tang H, et al. Kupffer cells in the liver. Compr Physiol, 2013, 3(2): 785-797.
18.	Capece D, Fischietti M, Verzella D, et al. The inflammatory microenvironment in hepatocellular carcinoma: a pivotal role for tumor-associated macrophages. Biomed Res Int, 2013, 2013: 187204.
19.	Katsumoto A, Lu H, Miranda AS, et al. Ontogeny and functions of central nervous system macrophages. J Immunol, 2014, 193(6): 2615-2621.
20.	Wu SY, Watabe K. The roles of microglia/macrophages in tumor progression of brain cancer and metastatic disease. Front Biosci (Landmark Ed), 2017, 22: 1805-1829.
21.	Hambardzumyan D, Gutmann DH, Kettenmann H. The role of microglia and macrophages in glioma maintenance and progression. Nat Neurosci, 2016, 19(1): 20-27.
22.	Watters JJ, Schartner JM, Badie B. Microglia function in brain tumors. J Neurosci Res, 2005, 81(3): 447-455.
23.	Coniglio SJ, Eugenin E, Dobrenis K, et al. Microglial stimulation of glioblastoma invasion involves epidermal growth factor receptor (EGFR) and colony stimulating factor 1 receptor (CSF-1R) signaling. Mol Med, 2012, 18(1): 519-527.
24.	Wang SC, Hong JH, Hsueh C, et al. Tumor-secreted SDF-1 promotes glioma invasiveness and TAM tropism toward hypoxia in a murine astrocytoma model. Lab Invest, 2012, 92(1): 151-162.
25.	Ku MC, Wolf SA, Respondek D, et al. GDNF mediates glioblastoma-induced microglia attraction but not astrogliosis. Acta Neuropathol, 2013, 125(4): 609-620.
26.	Held-Feindt J, Hattermann K, Müerköster SS, et al. CX3CR1 promotes recruitment of human glioma-infiltrating microglia/macrophages (GIMs). Exp Cell Res, 2010, 316(9): 1553-1566.
27.	Leung SY, Wong MP, Chung LP, et al. Monocyte chemoattractant protein-1 expression and macrophage infiltration in gliomas. Acta Neuropathol, 1997, 93(5): 518-527.
28.	Zhang J, Sarkar S, Cua R, et al. A dialog between glioma and microglia that promotes tumor invasiveness through the CCL2/CCR2/interleukin-6 axis. Carcinogenesis, 2012, 33(2): 312-319.
29.	Hambardzumyan D, Squatrito M, Holland EC. Radiation resistance and stem-like cells in brain tumors. Cancer Cell, 2006, 10(6): 454-456.
30.	Zhou W, Ke SQ, Huang Z, et al. Periostin secreted by glioblastoma stem cells recruits M2 tumour-associated macrophages and promotes malignant growth. Nat Cell Biol, 2015, 17(2): 170-182.
31.	Ye XZ, Xu SL, Xin YH, et al. Tumor-associated microglia/macrophages enhance the invasion of glioma stem-like cells via TGF-β1 signaling pathway. J Immunol, 2012, 189(1): 444-453.
32.	Yang L, Zhang Y. Tumor-associated macrophages: from basic research to clinical application. J Hematol Oncol, 2017, 10(1): 58.
33.	Chanmee T, Ontong P, Konno K, et al. Tumor-associated macrophages as major players in the tumor microenvironment. Cancers (Basel), 2014, 6(3): 1670-1690.
34.	Kogure A, Kosaka N, Ochiya T. Cross-talk between cancer cells and their neighbors via miRNA in extracellular vesicles: an emerging player in cancer metastasis. J Biomed Sci, 2019, 26(1): 7.
35.	Shirabe K, Mano Y, Muto J, et al. Role of tumor-associated macrophages in the progression of hepatocellular carcinoma. Surg Today, 2012, 42(1): 1-7.
36.	Tong H, Ke JQ, Jiang FZ, et al. Tumor-associated macrophage-derived CXCL8 could induce ERα suppression via HOXB13 in endometrial cancer. Cancer Lett, 2016, 376(1): 127-136.
37.	Lindsten T, Hedbrant A, Ramberg A, et al. Effect of macrophages on breast cancer cell proliferation, and on expression of hormone receptors, uPAR and HER-2. Int J Oncol, 2017, 51(1): 104-114.
38.	Arima K, Komohara Y, Bu L, et al. Downregulation of 15-hydroxyprostaglandin dehydrogenase by interleukin-1β from activated macrophages leads to poor prognosis in pancreatic cancer. Cancer Sci, 2018, 109(2): 462-470.
39.	Qian BZ, Pollard JW. Macrophage diversity enhances tumor progression and metastasis. Cell, 2010, 141(1): 39-51.
40.	Ayob AZ, Ramasamy TS. Cancer stem cells as key drivers of tumour progression. J Biomed Sci, 2018, 25(1): 20.
41.	Fan QM, Jing YY, Yu GF, et al. Tumor-associated macrophages promote cancer stem cell-like properties via transforming growth factor-beta1-induced epithelial-mesenchymal transition in hepatocellular carcinoma. Cancer Lett, 2014, 352(2): 160-168.
42.	Raghavan S, Mehta P, Xie Y, et al. Ovarian cancer stem cells and macrophages reciprocally interact through the WNT pathway to promote pro-tumoral and malignant phenotypes in 3D engineered microenvironments. J Immunother Cancer, 2019, 7(1): 190.
43.	Chen XW, Yu TJ, Zhang J, et al. CYP4A in tumor-associated macrophages promotes pre-metastatic niche formation and metastasis. Oncogene, 2017, 36(35): 5045-5057.
44.	Nielsen SR, Quaranta V, Linford A, et al. Macrophage-secreted granulin supports pancreatic cancer metastasis by inducing liver fibrosis. Nat Cell Biol, 2016, 18(5): 549-560.
45.	Celus W, Di Conza G, Oliveira AI, et al. Loss of caveolin-1 in metastasis-associated macrophages drives lung metastatic growth through increased angiogenesis. Cell Rep, 2017, 21(10): 2842-2854.
46.	Jung M, Ören B, Mora J, et al. Lipocalin 2 from macrophages stimulated by tumor cell-derived sphingosine 1-phosphate promotes lymphangiogenesis and tumor metastasis. Sci Signal, 2016, 9(434): ra64.
47.	Weiss JM, Ridnour LA, Back T, et al. Macrophage-dependent nitric oxide expression regulates tumor cell detachment and metastasis after IL-2/anti-CD40 immunotherapy. J Exp Med, 2010, 207(11): 2455-2467.
48.	Chen J, Yao Y, Gong C, et al. CCL18 from tumor-associated macrophages promotes breast cancer metastasis via PITPNM3. Cancer Cell, 2011, 19(4): 541-555.
49.	Leek RD, Hunt NC, Landers RJ, et al. Macrophage infiltration is associated with VEGF and EGFR expression in breast cancer. J Pathol, 2000, 190(4): 430-436.
50.	Sousa S, Määttä J. The role of tumour-associated macrophages in bone metastasis. J Bone Oncol, 2016, 5(3): 135-138.
51.	Wyckoff J, Wang W, Lin EY, et al. A paracrine loop between tumor cells and macrophages is required for tumor cell migration in mammary tumors. Cancer Res, 2004, 64(19): 7022-7029.
52.	Yao RR, Li JH, Zhang R, et al. M2-polarized tumor-associated macrophages facilitated migration and epithelial-mesenchymal transition of HCC cells via the TLR4/STAT3 signaling pathway. World J Surg Oncol, 2018, 16(1): 9.
53.	Liu CY, Xu JY, Shi XY, et al. M2-polarized tumor-associated macrophages promoted epithelial-mesenchymal transition in pancreatic cancer cells, partially through TLR4/IL-10 signaling pathway. Lab Invest, 2013, 93(7): 844-854.
54.	Cai J, Xia L, Li J, et al. Tumor-associated macrophages derived TGF-β‒induced epithelial to mesenchymal transition in colorectal cancer cells through smad 2, 3-4/snail signaling Pathway. Cancer Res Treat, 2019, 51(1): 252-266.
55.	Riabov V, Gudima A, Wang N, et al. Role of tumor associated macrophages in tumor angiogenesis and lymphangiogenesis. Front Physiol, 2014, 5: 75.
56.	Medrek C, Pontén F, Jirström K, et al. The presence of tumor associated macrophages in tumor stroma as a prognostic marker for breast cancer patients. BMC Cancer, 2012, 12: 306.
57.	Ferrer-Admetlla A, Sikora M, Laayouni H, et al. A natural history of FUT2 polymorphism in humans. Mol Biol Evol, 2009, 26(9): 1993-2003.
58.	Lu T, Ramakrishnan R, Altiok S, et al. Tumor-infiltrating myeloid cells induce tumor cell resistance to cytotoxic T cells in mice. J Clin Invest, 2011, 121(10): 4015-4029.
59.	Majmundar AJ, Wong WJ, Simon MC. Hypoxia-inducible factors and the response to hypoxic stress. Mol Cell, 2010, 40(2): 294-309.
60.	Lewis CE, De Palma M, Naldini L. Tie2-expressing monocytes and tumor angiogenesis: regulation by hypoxia and angiopoietin-2. Cancer Res, 2007, 67(18): 8429-8432.
61.	Wang X, Zhu Q, Lin Y, et al. Crosstalk between TEMs and endothelial cells modulates angiogenesis and metastasis via IGF1-IGF1R signalling in epithelial ovarian cancer. Br J Cancer, 2017, 117(9): 1371-1382.
62.	Farajzadeh Valilou S, Keshavarz-Fathi M, Silvestris N, et al. The role of inflammatory cytokines and tumor associated macrophages (TAMs) in microenvironment of pancreatic cancer. Cytokine Growth Factor Rev, 2018, 39: 46-61.
63.	Guo Q, Jin Z, Yuan Y, et al. New mechanisms of tumor-associated macrophages on promoting tumor progression: recent research advances and potential targets for tumor immunotherapy. J Immunol Res, 2016, 2016: 9720912.
64.	Lohela M, Casbon AJ, Olow A, et al. Intravital imaging reveals distinct responses of depleting dynamic tumor-associated macrophage and dendritic cell subpopulations. Proc Natl Acad Sci U S A, 2014, 111(47): E5086-E5095.
65.	Angelis A, Tordrup D, Kanavos P. Socio-economic burden of rare diseases: a systematic review of cost of illness evidence. Health Policy, 2015, 119(7): 964-979.
66.	Rodriguez PC, Quiceno DG, Zabaleta J, et al. Arginase I production in the tumor microenvironment by mature myeloid cells inhibits T-cell receptor expression and antigen-specific T-cell responses. Cancer Res, 2004, 64(16): 5839-5849.
67.	Kondo A, Yamashita T, Tamura H, et al. Interferon-gamma and tumor necrosis factor-alpha induce an immunoinhibitory molecule, B7-H1, via nuclear factor-kappaB activation in blasts in myelodysplastic syndromes. Blood, 2010, 116(7): 1124-1131.
68.	DeNardo DG, Brennan DJ, Rexhepaj E, et al. Leukocyte complexity predicts breast cancer survival and functionally regulates response to chemotherapy. Cancer Discov, 2011, 1(1): 54-67.
69.	Sanford DE, Belt BA, Panni RZ, et al. Inflammatory monocyte mobilization decreases patient survival in pancreatic cancer: a role for targeting the CCL2/CCR2 axis. Clin Cancer Res, 2013, 19(13): 3404-3415.
70.	Mantovani A, Marchesi F, Malesci A, et al. Tumour-associated macrophages as treatment targets in oncology. Nat Rev Clin Oncol, 2017, 14(7): 399-416.
71.	Ahn GO, Tseng D, Liao CH, et al. Inhibition of Mac-1 (CD11b/CD18) enhances tumor response to radiation by reducing myeloid cell recruitment. Proc Natl Acad Sci USA, 2010, 107(18): 8363-8368.
72.	Hegab AE, Ozaki M, Kameyama N, et al. Effect of FGF/FGFR pathway blocking on lung adenocarcinoma and its cancer-associated fibroblasts. J Pathol, 2019, 249(2): 193-205.
73.	Xia Y, Wei Y, Li ZY, et al. Catecholamines contribute to the neovascularization of lung cancer via tumor-associated macrophages. Brain Behav Immun, 2019, 81: 111-121.
74.	Piao C, Zhang WM, Li TT, et al. Complement 5a stimulates macrophage polarization and contributes to tumor metastases of colon cancer. Exp Cell Res, 2018, 366(2): 127-138.
75.	Hume DA, MacDonald KP. Therapeutic applications of macrophage colony-stimulating factor-1 (CSF-1) and antagonists of CSF-1 receptor (CSF-1R) signaling. Blood, 2012, 119(8): 1810-1820.
76.	Yan D, Kowal J, Akkari L, et al. Inhibition of colony stimulating factor-1 receptor abrogates microenvironment-mediated therapeutic resistance in gliomas. Oncogene, 2017, 36(43): 6049-6058.
77.	Moughon DL, He H, Schokrpur S, et al. Macrophage blockade using CSF1R inhibitors reverses the vascular leakage underlying malignant ascites in late-stage epithelial ovarian cancer. Cancer Res, 2015, 75(22): 4742-4752.
78.	Lu X, Meng T. Depletion of tumor-associated macrophages enhances the anti-tumor effect of docetaxel in a murine epithelial ovarian cancer. Immunobiology, 2019, 224(3): 355-361.
79.	Jeong H, Kim S, Hong BJ, et al. Tumor-associated macrophages enhance tumor hypoxia and aerobic glycolysis. Cancer Res, 2019, 79(4): 795-806.
80.	Germano G, Frapolli R, Belgiovine C, et al. Role of macrophage targeting in the antitumor activity of trabectedin. Cancer Cell, 2013, 23(2): 249-262.
81.	Laplagne C, Domagala M, Le Naour A, et al. Latest advances in targeting the tumor microenvironment for tumor suppression. Int J Mol Sci, 2019, 20(19): 4719.
82.	Georgoudaki AM, Prokopec KE, Boura VF, et al. Reprogramming tumor-associated macrophages by antibody targeting inhibits cancer progression and metastasis. Cell Rep, 2016, 15(9): 2000-2011.
83.	Sommariva M, Le Noci V, Storti C, et al. Activation of NK cell cytotoxicity by aerosolized CpG-ODN/poly(I: C) against lung melanoma metastases is mediated by alveolar macrophages. Cell Immunol, 2017, 313: 52-58.
84.	Halama N, Zoernig I, Berthel A, et al. Tumoral immune cell exploitation in colorectal cancer metastases can be targeted effectively by anti-CCR5 therapy in cancer patients. Cancer Cell, 2016, 29(4): 587-601.
85.	Long KB, Gladney WL, Tooker GM, et al. IFNγ and CCL2 cooperate to redirect tumor-infiltrating monocytes to degrade fibrosis and enhance chemotherapy efficacy in pancreatic carcinoma. Cancer Discov, 2016, 6(4): 400-413.
86.	Maeda A, Digifico E, Andon FT, et al. Poly(I: C) stimulation is superior than Imiquimod to induce the antitumoral functional profile of tumor-conditioned macrophages. Eur J Immunol, 2019, 49(5): 801-811.
87.	Mullins DW, Burger CJ, Elgert KD. Paclitaxel enhances macrophage IL-12 production in tumor-bearing hosts through nitric oxide. J Immunol, 1999, 162(11): 6811-6818.
88.	Andersen MN, Etzerodt A, Graversen JH, et al. STAT3 inhibition specifically in human monocytes and macrophages by CD163-targeted corosolic acid-containing liposomes. Cancer Immunol Immunother, 2019, 68(3): 489-502.
89.	Binnemars-Postma K, Bansal R, Storm G, et al. Targeting the Stat6 pathway in tumor-associated macrophages reduces tumor growth and metastatic niche formation in breast cancer. FASEB J, 2018, 32(2): 969-978.
90.	Ma B, Cheng H, Mu C, et al. The SIAH2-NRF1 axis spatially regulates tumor microenvironment remodeling for tumor progression. Nat Commun, 2019, 10(1): 1034.
91.	Verzella D, Bennett J, Fischietti M, et al. GADD45β loss ablates innate immunosuppression in cancer. Cancer Res, 2018, 78(5): 1275-1292.
92.	Wei X, Nie S, Liu H, et al. Angiopoietin-like protein 2 facilitates non-small cell lung cancer progression by promoting the polarization of M2 tumor-associated macrophages. Am J Cancer Res, 2017, 7(11): 2220-2233.
93.	Racioppi L, Nelson ER, Huang W, et al. CaMKK2 in myeloid cells is a key regulator of the immune-suppressive microenvironment in breast cancer. Nat Commun, 2019, 10(1): 2450.
94.	Zou Z, Yuan Z, Zhang Q, et al. Aurora kinase A inhibition-induced autophagy triggers drug resistance in breast cancer cells. Autophagy, 2012, 8(12): 1798-1810.
95.	Shan M, Qin J, Jin F, et al. Autophagy suppresses isoprenaline-induced M2 macrophage polarization via the ROS/ERK and mTOR signaling pathway. Free Radic Biol Med, 2017, 110: 432-443.
96.	Gordon SR, Maute RL, Dulken BW, et al. PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity. Nature, 2017, 545(7655): 495-499.

1. Roma-Rodrigues C, Mendes R, Baptista PV, et al. Targeting tumor microenvironment for cancer therapy. Int J Mol Sci, 2019, 20(4): 840.
2. Morrison C. Immuno-oncologists eye up macrophage targets. Nat Rev Drug Discov, 2016, 15(6): 373-374.
3. Long KB, Collier AI, Beatty GL. Macrophages: key orchestrators of a tumor microenvironment defined by therapeutic resistance. Mol Immunol, 2019, 110: 3-12.
4. Dehne N, Mora J, Namgaladze D, et al. Cancer cell and macrophage cross-talk in the tumor microenvironment. Curr Opin Pharmacol, 2017, 35: 12-19.
5. Ostuni R, Kratochvill F, Murray PJ, et al. Macrophages and cancer: from mechanisms to therapeutic implications. Trends Immunol, 2015, 36(4): 229-239.
6. Jeannin P, Paolini L, Adam C, et al. The roles of CSFs on the functional polarization of tumor-associated macrophages. FEBS J, 2018, 285(4): 680-699.
7. Salmaninejad A, Valilou SF, Soltani A, et al. Tumor-associated macrophages: role in cancer development and therapeutic implications. Cell Oncol (Dordr), 2019, 42(5): 591-608.
8. Sica A, Schioppa T, Mantovani A, et al. Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression: potential targets of anti-cancer therapy. Eur J Cancer, 2006, 42(6): 717-727.
9. Netea-Maier RT, Smit JWA, Netea MG. Metabolic changes in tumor cells and tumor-associated macrophages: a mutual relationship. Cancer Lett, 2018, 413: 102-109.
10. Lewis CE, Pollard JW. Distinct role of macrophages in different tumor microenvironments. Cancer Res, 2006, 66(2): 605-612.
11. Kielbassa K, Vegna S, Ramirez C, et al. Understanding the origin and diversity of macrophages to tailor their targeting in solid cancers. Front Immunol, 2019, 10: 2215.
12. van Eeden SF, Tan WC, Suwa T, et al. Cytokines involved in the systemic inflammatory response induced by exposure to particulate matter air pollutants (PM10). Am J Respir Crit Care Med, 2001, 164(5): 826-830.
13. Hamilton G, Rath B, Klameth L, et al. Small cell lung cancer: recruitment of macrophages by circulating tumor cells. Oncoimmunology, 2015, 5(3): e1093277.
14. Kortlever RM, Sodir NM, Wilson CH, et al. Myc cooperates with ras by programming inflammation and immune suppression. Cell, 2017, 171(6): 1301-1315. e14.
15. Krenkel O, Tacke F. Liver macrophages in tissue homeostasis and disease. Nat Rev Immunol, 2017, 17(5): 306-321.
16. Yu LX, Ling Y, Wang HY. Role of nonresolving inflammation in hepatocellular carcinoma development and progression. NPJ Precis Oncol, 2018, 2(1): 6.
17. Dixon LJ, Barnes M, Tang H, et al. Kupffer cells in the liver. Compr Physiol, 2013, 3(2): 785-797.
18. Capece D, Fischietti M, Verzella D, et al. The inflammatory microenvironment in hepatocellular carcinoma: a pivotal role for tumor-associated macrophages. Biomed Res Int, 2013, 2013: 187204.
19. Katsumoto A, Lu H, Miranda AS, et al. Ontogeny and functions of central nervous system macrophages. J Immunol, 2014, 193(6): 2615-2621.
20. Wu SY, Watabe K. The roles of microglia/macrophages in tumor progression of brain cancer and metastatic disease. Front Biosci (Landmark Ed), 2017, 22: 1805-1829.
21. Hambardzumyan D, Gutmann DH, Kettenmann H. The role of microglia and macrophages in glioma maintenance and progression. Nat Neurosci, 2016, 19(1): 20-27.
22. Watters JJ, Schartner JM, Badie B. Microglia function in brain tumors. J Neurosci Res, 2005, 81(3): 447-455.
23. Coniglio SJ, Eugenin E, Dobrenis K, et al. Microglial stimulation of glioblastoma invasion involves epidermal growth factor receptor (EGFR) and colony stimulating factor 1 receptor (CSF-1R) signaling. Mol Med, 2012, 18(1): 519-527.
24. Wang SC, Hong JH, Hsueh C, et al. Tumor-secreted SDF-1 promotes glioma invasiveness and TAM tropism toward hypoxia in a murine astrocytoma model. Lab Invest, 2012, 92(1): 151-162.
25. Ku MC, Wolf SA, Respondek D, et al. GDNF mediates glioblastoma-induced microglia attraction but not astrogliosis. Acta Neuropathol, 2013, 125(4): 609-620.
26. Held-Feindt J, Hattermann K, Müerköster SS, et al. CX3CR1 promotes recruitment of human glioma-infiltrating microglia/macrophages (GIMs). Exp Cell Res, 2010, 316(9): 1553-1566.
27. Leung SY, Wong MP, Chung LP, et al. Monocyte chemoattractant protein-1 expression and macrophage infiltration in gliomas. Acta Neuropathol, 1997, 93(5): 518-527.
28. Zhang J, Sarkar S, Cua R, et al. A dialog between glioma and microglia that promotes tumor invasiveness through the CCL2/CCR2/interleukin-6 axis. Carcinogenesis, 2012, 33(2): 312-319.
29. Hambardzumyan D, Squatrito M, Holland EC. Radiation resistance and stem-like cells in brain tumors. Cancer Cell, 2006, 10(6): 454-456.
30. Zhou W, Ke SQ, Huang Z, et al. Periostin secreted by glioblastoma stem cells recruits M2 tumour-associated macrophages and promotes malignant growth. Nat Cell Biol, 2015, 17(2): 170-182.
31. Ye XZ, Xu SL, Xin YH, et al. Tumor-associated microglia/macrophages enhance the invasion of glioma stem-like cells via TGF-β1 signaling pathway. J Immunol, 2012, 189(1): 444-453.
32. Yang L, Zhang Y. Tumor-associated macrophages: from basic research to clinical application. J Hematol Oncol, 2017, 10(1): 58.
33. Chanmee T, Ontong P, Konno K, et al. Tumor-associated macrophages as major players in the tumor microenvironment. Cancers (Basel), 2014, 6(3): 1670-1690.
34. Kogure A, Kosaka N, Ochiya T. Cross-talk between cancer cells and their neighbors via miRNA in extracellular vesicles: an emerging player in cancer metastasis. J Biomed Sci, 2019, 26(1): 7.
35. Shirabe K, Mano Y, Muto J, et al. Role of tumor-associated macrophages in the progression of hepatocellular carcinoma. Surg Today, 2012, 42(1): 1-7.
36. Tong H, Ke JQ, Jiang FZ, et al. Tumor-associated macrophage-derived CXCL8 could induce ERα suppression via HOXB13 in endometrial cancer. Cancer Lett, 2016, 376(1): 127-136.
37. Lindsten T, Hedbrant A, Ramberg A, et al. Effect of macrophages on breast cancer cell proliferation, and on expression of hormone receptors, uPAR and HER-2. Int J Oncol, 2017, 51(1): 104-114.
38. Arima K, Komohara Y, Bu L, et al. Downregulation of 15-hydroxyprostaglandin dehydrogenase by interleukin-1β from activated macrophages leads to poor prognosis in pancreatic cancer. Cancer Sci, 2018, 109(2): 462-470.
39. Qian BZ, Pollard JW. Macrophage diversity enhances tumor progression and metastasis. Cell, 2010, 141(1): 39-51.
40. Ayob AZ, Ramasamy TS. Cancer stem cells as key drivers of tumour progression. J Biomed Sci, 2018, 25(1): 20.
41. Fan QM, Jing YY, Yu GF, et al. Tumor-associated macrophages promote cancer stem cell-like properties via transforming growth factor-beta1-induced epithelial-mesenchymal transition in hepatocellular carcinoma. Cancer Lett, 2014, 352(2): 160-168.
42. Raghavan S, Mehta P, Xie Y, et al. Ovarian cancer stem cells and macrophages reciprocally interact through the WNT pathway to promote pro-tumoral and malignant phenotypes in 3D engineered microenvironments. J Immunother Cancer, 2019, 7(1): 190.
43. Chen XW, Yu TJ, Zhang J, et al. CYP4A in tumor-associated macrophages promotes pre-metastatic niche formation and metastasis. Oncogene, 2017, 36(35): 5045-5057.
44. Nielsen SR, Quaranta V, Linford A, et al. Macrophage-secreted granulin supports pancreatic cancer metastasis by inducing liver fibrosis. Nat Cell Biol, 2016, 18(5): 549-560.
45. Celus W, Di Conza G, Oliveira AI, et al. Loss of caveolin-1 in metastasis-associated macrophages drives lung metastatic growth through increased angiogenesis. Cell Rep, 2017, 21(10): 2842-2854.
46. Jung M, Ören B, Mora J, et al. Lipocalin 2 from macrophages stimulated by tumor cell-derived sphingosine 1-phosphate promotes lymphangiogenesis and tumor metastasis. Sci Signal, 2016, 9(434): ra64.
47. Weiss JM, Ridnour LA, Back T, et al. Macrophage-dependent nitric oxide expression regulates tumor cell detachment and metastasis after IL-2/anti-CD40 immunotherapy. J Exp Med, 2010, 207(11): 2455-2467.
48. Chen J, Yao Y, Gong C, et al. CCL18 from tumor-associated macrophages promotes breast cancer metastasis via PITPNM3. Cancer Cell, 2011, 19(4): 541-555.
49. Leek RD, Hunt NC, Landers RJ, et al. Macrophage infiltration is associated with VEGF and EGFR expression in breast cancer. J Pathol, 2000, 190(4): 430-436.
50. Sousa S, Määttä J. The role of tumour-associated macrophages in bone metastasis. J Bone Oncol, 2016, 5(3): 135-138.
51. Wyckoff J, Wang W, Lin EY, et al. A paracrine loop between tumor cells and macrophages is required for tumor cell migration in mammary tumors. Cancer Res, 2004, 64(19): 7022-7029.
52. Yao RR, Li JH, Zhang R, et al. M2-polarized tumor-associated macrophages facilitated migration and epithelial-mesenchymal transition of HCC cells via the TLR4/STAT3 signaling pathway. World J Surg Oncol, 2018, 16(1): 9.
53. Liu CY, Xu JY, Shi XY, et al. M2-polarized tumor-associated macrophages promoted epithelial-mesenchymal transition in pancreatic cancer cells, partially through TLR4/IL-10 signaling pathway. Lab Invest, 2013, 93(7): 844-854.
54. Cai J, Xia L, Li J, et al. Tumor-associated macrophages derived TGF-β‒induced epithelial to mesenchymal transition in colorectal cancer cells through smad 2, 3-4/snail signaling Pathway. Cancer Res Treat, 2019, 51(1): 252-266.
55. Riabov V, Gudima A, Wang N, et al. Role of tumor associated macrophages in tumor angiogenesis and lymphangiogenesis. Front Physiol, 2014, 5: 75.
56. Medrek C, Pontén F, Jirström K, et al. The presence of tumor associated macrophages in tumor stroma as a prognostic marker for breast cancer patients. BMC Cancer, 2012, 12: 306.
57. Ferrer-Admetlla A, Sikora M, Laayouni H, et al. A natural history of FUT2 polymorphism in humans. Mol Biol Evol, 2009, 26(9): 1993-2003.
58. Lu T, Ramakrishnan R, Altiok S, et al. Tumor-infiltrating myeloid cells induce tumor cell resistance to cytotoxic T cells in mice. J Clin Invest, 2011, 121(10): 4015-4029.
59. Majmundar AJ, Wong WJ, Simon MC. Hypoxia-inducible factors and the response to hypoxic stress. Mol Cell, 2010, 40(2): 294-309.
60. Lewis CE, De Palma M, Naldini L. Tie2-expressing monocytes and tumor angiogenesis: regulation by hypoxia and angiopoietin-2. Cancer Res, 2007, 67(18): 8429-8432.
61. Wang X, Zhu Q, Lin Y, et al. Crosstalk between TEMs and endothelial cells modulates angiogenesis and metastasis via IGF1-IGF1R signalling in epithelial ovarian cancer. Br J Cancer, 2017, 117(9): 1371-1382.
62. Farajzadeh Valilou S, Keshavarz-Fathi M, Silvestris N, et al. The role of inflammatory cytokines and tumor associated macrophages (TAMs) in microenvironment of pancreatic cancer. Cytokine Growth Factor Rev, 2018, 39: 46-61.
63. Guo Q, Jin Z, Yuan Y, et al. New mechanisms of tumor-associated macrophages on promoting tumor progression: recent research advances and potential targets for tumor immunotherapy. J Immunol Res, 2016, 2016: 9720912.
64. Lohela M, Casbon AJ, Olow A, et al. Intravital imaging reveals distinct responses of depleting dynamic tumor-associated macrophage and dendritic cell subpopulations. Proc Natl Acad Sci U S A, 2014, 111(47): E5086-E5095.
65. Angelis A, Tordrup D, Kanavos P. Socio-economic burden of rare diseases: a systematic review of cost of illness evidence. Health Policy, 2015, 119(7): 964-979.
66. Rodriguez PC, Quiceno DG, Zabaleta J, et al. Arginase I production in the tumor microenvironment by mature myeloid cells inhibits T-cell receptor expression and antigen-specific T-cell responses. Cancer Res, 2004, 64(16): 5839-5849.
67. Kondo A, Yamashita T, Tamura H, et al. Interferon-gamma and tumor necrosis factor-alpha induce an immunoinhibitory molecule, B7-H1, via nuclear factor-kappaB activation in blasts in myelodysplastic syndromes. Blood, 2010, 116(7): 1124-1131.
68. DeNardo DG, Brennan DJ, Rexhepaj E, et al. Leukocyte complexity predicts breast cancer survival and functionally regulates response to chemotherapy. Cancer Discov, 2011, 1(1): 54-67.
69. Sanford DE, Belt BA, Panni RZ, et al. Inflammatory monocyte mobilization decreases patient survival in pancreatic cancer: a role for targeting the CCL2/CCR2 axis. Clin Cancer Res, 2013, 19(13): 3404-3415.
70. Mantovani A, Marchesi F, Malesci A, et al. Tumour-associated macrophages as treatment targets in oncology. Nat Rev Clin Oncol, 2017, 14(7): 399-416.
71. Ahn GO, Tseng D, Liao CH, et al. Inhibition of Mac-1 (CD11b/CD18) enhances tumor response to radiation by reducing myeloid cell recruitment. Proc Natl Acad Sci USA, 2010, 107(18): 8363-8368.
72. Hegab AE, Ozaki M, Kameyama N, et al. Effect of FGF/FGFR pathway blocking on lung adenocarcinoma and its cancer-associated fibroblasts. J Pathol, 2019, 249(2): 193-205.
73. Xia Y, Wei Y, Li ZY, et al. Catecholamines contribute to the neovascularization of lung cancer via tumor-associated macrophages. Brain Behav Immun, 2019, 81: 111-121.
74. Piao C, Zhang WM, Li TT, et al. Complement 5a stimulates macrophage polarization and contributes to tumor metastases of colon cancer. Exp Cell Res, 2018, 366(2): 127-138.
75. Hume DA, MacDonald KP. Therapeutic applications of macrophage colony-stimulating factor-1 (CSF-1) and antagonists of CSF-1 receptor (CSF-1R) signaling. Blood, 2012, 119(8): 1810-1820.
76. Yan D, Kowal J, Akkari L, et al. Inhibition of colony stimulating factor-1 receptor abrogates microenvironment-mediated therapeutic resistance in gliomas. Oncogene, 2017, 36(43): 6049-6058.
77. Moughon DL, He H, Schokrpur S, et al. Macrophage blockade using CSF1R inhibitors reverses the vascular leakage underlying malignant ascites in late-stage epithelial ovarian cancer. Cancer Res, 2015, 75(22): 4742-4752.
78. Lu X, Meng T. Depletion of tumor-associated macrophages enhances the anti-tumor effect of docetaxel in a murine epithelial ovarian cancer. Immunobiology, 2019, 224(3): 355-361.
79. Jeong H, Kim S, Hong BJ, et al. Tumor-associated macrophages enhance tumor hypoxia and aerobic glycolysis. Cancer Res, 2019, 79(4): 795-806.
80. Germano G, Frapolli R, Belgiovine C, et al. Role of macrophage targeting in the antitumor activity of trabectedin. Cancer Cell, 2013, 23(2): 249-262.
81. Laplagne C, Domagala M, Le Naour A, et al. Latest advances in targeting the tumor microenvironment for tumor suppression. Int J Mol Sci, 2019, 20(19): 4719.
82. Georgoudaki AM, Prokopec KE, Boura VF, et al. Reprogramming tumor-associated macrophages by antibody targeting inhibits cancer progression and metastasis. Cell Rep, 2016, 15(9): 2000-2011.
83. Sommariva M, Le Noci V, Storti C, et al. Activation of NK cell cytotoxicity by aerosolized CpG-ODN/poly(I: C) against lung melanoma metastases is mediated by alveolar macrophages. Cell Immunol, 2017, 313: 52-58.
84. Halama N, Zoernig I, Berthel A, et al. Tumoral immune cell exploitation in colorectal cancer metastases can be targeted effectively by anti-CCR5 therapy in cancer patients. Cancer Cell, 2016, 29(4): 587-601.
85. Long KB, Gladney WL, Tooker GM, et al. IFNγ and CCL2 cooperate to redirect tumor-infiltrating monocytes to degrade fibrosis and enhance chemotherapy efficacy in pancreatic carcinoma. Cancer Discov, 2016, 6(4): 400-413.
86. Maeda A, Digifico E, Andon FT, et al. Poly(I: C) stimulation is superior than Imiquimod to induce the antitumoral functional profile of tumor-conditioned macrophages. Eur J Immunol, 2019, 49(5): 801-811.
87. Mullins DW, Burger CJ, Elgert KD. Paclitaxel enhances macrophage IL-12 production in tumor-bearing hosts through nitric oxide. J Immunol, 1999, 162(11): 6811-6818.
88. Andersen MN, Etzerodt A, Graversen JH, et al. STAT3 inhibition specifically in human monocytes and macrophages by CD163-targeted corosolic acid-containing liposomes. Cancer Immunol Immunother, 2019, 68(3): 489-502.
89. Binnemars-Postma K, Bansal R, Storm G, et al. Targeting the Stat6 pathway in tumor-associated macrophages reduces tumor growth and metastatic niche formation in breast cancer. FASEB J, 2018, 32(2): 969-978.
90. Ma B, Cheng H, Mu C, et al. The SIAH2-NRF1 axis spatially regulates tumor microenvironment remodeling for tumor progression. Nat Commun, 2019, 10(1): 1034.
91. Verzella D, Bennett J, Fischietti M, et al. GADD45β loss ablates innate immunosuppression in cancer. Cancer Res, 2018, 78(5): 1275-1292.
92. Wei X, Nie S, Liu H, et al. Angiopoietin-like protein 2 facilitates non-small cell lung cancer progression by promoting the polarization of M2 tumor-associated macrophages. Am J Cancer Res, 2017, 7(11): 2220-2233.
93. Racioppi L, Nelson ER, Huang W, et al. CaMKK2 in myeloid cells is a key regulator of the immune-suppressive microenvironment in breast cancer. Nat Commun, 2019, 10(1): 2450.
94. Zou Z, Yuan Z, Zhang Q, et al. Aurora kinase A inhibition-induced autophagy triggers drug resistance in breast cancer cells. Autophagy, 2012, 8(12): 1798-1810.
95. Shan M, Qin J, Jin F, et al. Autophagy suppresses isoprenaline-induced M2 macrophage polarization via the ROS/ERK and mTOR signaling pathway. Free Radic Biol Med, 2017, 110: 432-443.
96. Gordon SR, Maute RL, Dulken BW, et al. PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity. Nature, 2017, 545(7655): 495-499.

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