Abstract
Cancer tissues are invariably infiltrated by cells of the immune system, and macrophages constitute the major portion of these. Experimental pieces of evidence demonstrated that macrophages highly infiltrate the tumour tissues of colorectal cancer. Although these tumour-associated macrophages (TAM) are sought to exert their function to control tumour growth, under influence of the unique constitution of the tumour microenvironment (TME), they start favouring various hallmarks of cancer. Contributing to angiogenesis, metastasis, matrix remodelling, and chemoresistance, these TAM also hinder the antitumour immune response of other immune cells. Targeting approaches have been devised to break the contribution of TAM in tumour progression. Moreover, despite their functional activation, TAMs preserve their plasticity and responsiveness to various stimulants. Reprogramming of TAM is achieved through blocking the pro-tumour TAM favouring signals or stimulating the antitumour activating receptors. Nevertheless, epigenomic and microRNAs manipulation also achieve reprogramming of antitumour macrophage activation. Even TME manipulative strategies split immunosuppressive conduct of tumour tissue. Collectively, the versatile nature of macrophages makes it a good candidate for targeting in therapeutic interventions. Targeting TAM not only improves the immune response of macrophages and other immune cells but it also cooperates with chemotherapeutic interventions.
A. Mehta and V.K. Soni contributed equally to this work as first authors.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Afik, R., Zigmond, E., Vugman, M., Klepfish, M., Shimshoni, E., Pasmanik-Chor, M., … Varol, C. (2016). Tumor macrophages are pivotal constructors of tumor collagenous matrix. The Journal of Experimental Medicine, 213(11), 2315–2331. https://doi.org/10.1084/jem.20151193
Ahn, G. O., & Brown, J. M. (2008). Matrix metalloproteinase-9 is required for tumor vasculogenesis but not for angiogenesis: Role of bone marrow-derived myelomonocytic cells. Cancer Cell, 13(3), 193–205. https://doi.org/10.1016/j.ccr.2007.11.032
Al, B. B., Alan, P. V., Mahmoud, M. A.-H., Lynette, C., Yi-Jen, C., Kristen, K. C., … Deborah, A. F.-C. (2018). NCCN guidelines insights: Colon cancer, version 2.2018. Journal of the National Comprehensive Cancer Network, 16(4), 359–369. https://doi.org/10.6004/jnccn.2018.0021
Andreu, P., Johansson, M., Affara, N. I., Pucci, F., Tan, T., Junankar, S., … Coussens, L. M. (2010). FcRgamma activation regulates inflammation-associated squamous carcinogenesis. Cancer Cell, 17(2), 121–134. https://doi.org/10.1016/j.ccr.2009.12.019
Anfray, C., Ummarino, A., Andón, F. T., & Allavena, P. (2019). Current strategies to target tumor-associated-macrophages to improve anti-tumor immune responses. Cell, 9(1), 46. https://doi.org/10.3390/cells9010046
Angelillo-Scherrer, A., Burnier, L., Lambrechts, D., Fish, R. J., Tjwa, M., Plaisance, S., … Carmeliet, P. (2008). Role of Gas6 in erythropoiesis and anemia in mice. The Journal of Clinical Investigation, 118(2), 583–596. https://doi.org/10.1172/JCI30375
Argyle, D., & Kitamura, T. (2018). Targeting macrophage-recruiting chemokines as a novel therapeutic strategy to prevent the progression of solid tumors. Frontiers in Immunology, 9, 2629–2629. https://doi.org/10.3389/fimmu.2018.02629
Badawi, M. A., Abouelfadl, D. M., El-Sharkawy, S. L., El-Aal, W. E. A., & Abbas, N. F. (2015). Tumor-associated macrophage (TAM) and angiogenesis in human colon carcinoma. Open Access Macedonian Journal of Medical Sciences, 3(2), 209–214. https://doi.org/10.3889/oamjms.2015.044
Baer, C., Squadrito, M. L., Laoui, D., Thompson, D., Hansen, S. K., Kiialainen, A., ... & De Palma, M. (2016). Suppression of microRNA activity amplifies IFN-γ-induced macrophage activation and promotes anti-tumour immunity. Nature cell biology, 18(7), 790–802.
Balkwill, F., & Mantovani, A. (2001). Inflammation and cancer: Back to Virchow? The Lancet, 357(9255), 539–545. https://doi.org/10.1016/S0140-6736(00)04046-0
Bingle, L., Brown, N. J., & Lewis, C. E. (2002). The role of tumour-associated macrophages in tumour progression: Implications for new anticancer therapies. The Journal of Pathology, 196(3), 254–265. https://doi.org/10.1002/path.1027
Bluff, J. E., Menakuru, S. R., Cross, S. S., Higham, S. E., Balasubramanian, S. P., Brown, N. J., … Staton, C. A. (2009). Angiogenesis is associated with the onset of hyperplasia in human ductal breast disease. British Journal of Cancer, 101(4), 666–672. https://doi.org/10.1038/sj.bjc.6605196
Cassetta, L., & Pollard, J. W. (2018). Targeting macrophages: Therapeutic approaches in cancer. Nature Reviews Drug Discovery, 17(12), 887–904. https://doi.org/10.1038/nrd.2018.169
Chávez-Galán, L., Olleros, M. L., Vesin, D., & Garcia, I. (2015). Much more than M1 and M2 macrophages, there are also CD169(+) and TCR(+) macrophages. Frontiers in Immunology, 6, 263–263. https://doi.org/10.3389/fimmu.2015.00263
Condeelis, J., & Pollard, J. W. (2006). Macrophages: Obligate partners for tumor cell migration, invasion, and metastasis. Cell, 124(2), 263–266. https://doi.org/10.1016/j.cell.2006.01.007
Coussens, L. M., & Werb, Z. (2002). Inflammation and cancer. Nature, 420(6917), 860–867. https://doi.org/10.1038/nature01322
Coward, J., Kulbe, H., Chakravarty, P., Leader, D., Vassileva, V., Leinster, D. A., … Balkwill, F. R. (2011). Interleukin-6 as a therapeutic target in human ovarian cancer. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 17(18), 6083–6096. https://doi.org/10.1158/1078-0432.CCR-11-0945
Curiel, T. J., Coukos, G., Zou, L., Alvarez, X., Cheng, P., Mottram, P., … Zou, W. (2004). Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nature Medicine, 10(9), 942–949. https://doi.org/10.1038/nm1093
DeNardo, D. G., Barreto, J. B., Andreu, P., Vasquez, L., Tawfik, D., Kolhatkar, N., & Coussens, L. M. (2009). CD4(+) T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumor properties of macrophages. Cancer Cell, 16(2), 91–102. https://doi.org/10.1016/j.ccr.2009.06.018
Du, R., Lu, K. V., Petritsch, C., Liu, P., Ganss, R., Passegué, E., … Bergers, G. (2008). HIF1alpha induces the recruitment of bone marrow-derived vascular modulatory cells to regulate tumor angiogenesis and invasion. Cancer Cell, 13(3), 206–220. https://doi.org/10.1016/j.ccr.2008.01.034
Erler, J. T., Bennewith, K. L., Cox, T. R., Lang, G., Bird, D., Koong, A., … Giaccia, A. J. (2009). Hypoxia-induced lysyl oxidase is a critical mediator of bone marrow cell recruitment to form the premetastatic niche. Cancer Cell, 15(1), 35–44. https://doi.org/10.1016/j.ccr.2008.11.012
Erler, J. T., & Weaver, V. M. (2009). Three-dimensional context regulation of metastasis. Clinical & Experimental Metastasis, 26(1), 35–49. https://doi.org/10.1007/s10585-008-9209-8
Fernández-Fernández, L., Bellido-MartÃn, L., & GarcÃa de Frutos, P. (2008). Growth arrest-specific gene 6 (GAS6). Thrombosis and Haemostasis, 100(10), 604–610. https://doi.org/10.1160/TH08-04-0253
Folkman, J. (2002). Role of angiogenesis in tumor growth and metastasis. Seminars in Oncology, 29(6, Supplement 16), 15–18. https://doi.org/10.1016/S0093-7754(02)70065-1
Forssell, J., Öberg, Å., Henriksson, M. L., Stenling, R., Jung, A., & Palmqvist, R. (2007). High macrophage infiltration along the tumor front correlates with improved survival in colon cancer. Clinical Cancer Research, 13(5), 1472. https://doi.org/10.1158/1078-0432.CCR-06-2073
Franklin, R. A., Liao, W., Sarkar, A., Kim, M. V., Bivona, M. R., Liu, K., … Li, M. O. (2014). The cellular and molecular origin of tumor-associated macrophages. Science (New York, N.Y.), 344(6186), 921–925. https://doi.org/10.1126/science.1252510
Gabrilovich, D. I., Ostrand-Rosenberg, S., & Bronte, V. (2012). Coordinated regulation of myeloid cells by tumours. Nature Reviews Immunology, 12(4), 253–268. https://doi.org/10.1038/nri3175
Georgoudaki, A.-M., Prokopec, K. E., Boura, V. F., Hellqvist, E., Sohn, S., Östling, J., … Karlsson, M. C. I. (2016). Reprogramming tumor-associated macrophages by antibody targeting inhibits cancer progression and metastasis. Cell Reports, 15(9), 2000–2011. https://doi.org/10.1016/j.celrep.2016.04.084
Germano, G., Frapolli, R., Simone, M., Tavecchio, M., Erba, E., Pesce, S., … Allavena, P. (2010). Antitumor and anti-inflammatory effects of trabectedin on human myxoid liposarcoma cells. Cancer Research, 70(6), 2235–2244. https://doi.org/10.1158/0008-5472.can-09-2335
Gilkes, D. M., Semenza, G. L., & Wirtz, D. (2014). Hypoxia and the extracellular matrix: Drivers of tumour metastasis. Nature Reviews Cancer, 14(6), 430–439. https://doi.org/10.1038/nrc3726
Gocheva, V., Wang, H.-W., Gadea, B. B., Shree, T., Hunter, K. E., Garfall, A. L., … Joyce, J. A. (2010). IL-4 induces cathepsin protease activity in tumor-associated macrophages to promote cancer growth and invasion. Genes & Development, 24(3), 241–255. https://doi.org/10.1101/gad.1874010
Grégoire, H., Roncali, L., Rousseau, A., Chérel, M., Delneste, Y., Jeannin, P., … Garcion, E. (2020). Targeting tumor associated macrophages to overcome conventional treatment resistance in glioblastoma. Frontiers in Pharmacology, 11, 368–368. https://doi.org/10.3389/fphar.2020.00368
Guerriero, J. L., Sotayo, A., Ponichtera, H. E., Castrillon, J. A., Pourzia, A. L., Schad, S., … Letai, A. (2017). Class IIa HDAC inhibition reduces breast tumours and metastases through anti-tumour macrophages. Nature, 543(7645), 428–432. https://doi.org/10.1038/nature21409
Guillon, J., Petit, C., Moreau, M., Toutain, B., Henry, C., Roché, H., … Coqueret, O. (2019). Regulation of senescence escape by TSP1 and CD47 following chemotherapy treatment. Cell Death & Disease, 10(3), 199. https://doi.org/10.1038/s41419-019-1406-7
Gupta, G. P., & Massagué, J. (2006). Cancer metastasis: Building a framework. Cell, 127(4), 679–695. https://doi.org/10.1016/j.cell.2006.11.001
Hagemann, T., Wilson, J., Kulbe, H., Li, N. F., Leinster, D. A., Charles, K., … Balkwill, F. R. (2005). Macrophages induce invasiveness of epithelial cancer cells via NF-κB and JNK. The Journal of Immunology, 175(2), 1197. https://doi.org/10.4049/jimmunol.175.2.1197
Hanahan, D., & Weinberg, R. A. (2000). The hallmarks of cancer. Cell, 100(1), 57–70. https://doi.org/10.1016/S0092-8674(00)81683-9
Hiratsuka, S., Watanabe, A., Aburatani, H., & Maru, Y. (2006). Tumour-mediated upregulation of chemoattractants and recruitment of myeloid cells predetermines lung metastasis. Nature Cell Biology, 8(12), 1369–1375. https://doi.org/10.1038/ncb1507
Holohan, C., Van Schaeybroeck, S., Longley, D. B., & Johnston, P. G. (2013). Cancer drug resistance: An evolving paradigm. Nature Reviews Cancer, 13(10), 714–726. https://doi.org/10.1038/nrc3599
Hughes, R., Qian, B.-Z., Rowan, C., Muthana, M., Keklikoglou, I., Olson, O. C., … Lewis, C. E. (2015). Perivascular M2 macrophages stimulate tumor relapse after chemotherapy. Cancer Research, 75(17), 3479–3491. https://doi.org/10.1158/0008-5472.can-14-3587
Ireland, L., Santos, A., Ahmed, M. S., Rainer, C., Nielsen, S. R., Quaranta, V., … Mielgo, A. (2016). Chemoresistance in pancreatic cancer is driven by stroma-derived insulin-like growth factors. Cancer Research, 76(23), 6851–6863. https://doi.org/10.1158/0008-5472.CAN-16-1201
Junttila, M. R., & de Sauvage, F. J. (2013). Influence of tumour micro-environment heterogeneity on therapeutic response. Nature, 501(7467), 346–354. https://doi.org/10.1038/nature12626
Kaneda, M. M., Messer, K. S., Ralainirina, N., Li, H., Leem, C. J., Gorjestani, S., … Varner, J. A. (2016). PI3Kγ is a molecular switch that controls immune suppression. Nature, 539(7629), 437–442. https://doi.org/10.1038/nature19834
Kaplan, R. N., Riba, R. D., Zacharoulis, S., Bramley, A. H., Vincent, L., Costa, C., … Lyden, D. (2005). VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature, 438(7069), 820–827. https://doi.org/10.1038/nature04186
Kim, S., Takahashi, H., Lin, W.-W., Descargues, P., Grivennikov, S., Kim, Y., … Karin, M. (2009). Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis. Nature, 457(7225), 102–106. https://doi.org/10.1038/nature07623
Komohara, Y., Jinushi, M., & Takeya, M. (2014). Clinical significance of macrophage heterogeneity in human malignant tumors. Cancer Science, 105(1), 1–8. https://doi.org/10.1111/cas.12314
Kuang, D.-M., Zhao, Q., Peng, C., Xu, J., Zhang, J.-P., Wu, C., & Zheng, L. (2009). Activated monocytes in peritumoral stroma of hepatocellular carcinoma foster immune privilege and disease progression through PD-L1. The Journal of Experimental Medicine, 206(6), 1327–1337. https://doi.org/10.1084/jem.20082173
Liguori, M., Solinas, G., Germano, G., Mantovani, A., & Allavena, P. (2011). Tumor-associated macrophages as incessant builders and destroyers of the cancer stroma. Cancers, 3(4), 3740–3761. https://doi.org/10.3390/cancers3043740
Lin, E. Y., Nguyen, A. V., Russell, R. G., & Pollard, J. W. (2001). Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy. The Journal of Experimental Medicine, 193(6), 727–740. https://doi.org/10.1084/jem.193.6.727
Liu, C., Yu, S., Kappes, J., Wang, J., Grizzle, W. E., Zinn, K. R., & Zhang, H.-G. (2007). Expansion of spleen myeloid suppressor cells represses NK cell cytotoxicity in tumor-bearing host. Blood, 109(10), 4336–4342. https://doi.org/10.1182/blood-2006-09-046201
Liu, Y., & Cao, X. (2015). The origin and function of tumor-associated macrophages. Cellular & Molecular Immunology, 12(1), 1–4. https://doi.org/10.1038/cmi.2014.83
Lu, T., Ramakrishnan, R., Altiok, S., Youn, J.-I., Cheng, P., Celis, E., … Gabrilovich, D. (2011). Tumor-infiltrating myeloid cells induce tumor cell resistance to cytotoxic T cells in mice. The Journal of Clinical Investigation, 121(10), 4015–4029. https://doi.org/10.1172/JCI45862
Mantovani, A., Allavena, P., Sica, A., & Balkwill, F. (2008). Cancer-related inflammation. Nature, 454(7203), 436–444. https://doi.org/10.1038/nature07205
Mantovani, A., & Sica, A. (2010). Macrophages, innate immunity and cancer: Balance, tolerance, and diversity. Current Opinion in Immunology, 22(2), 231–237. https://doi.org/10.1016/j.coi.2010.01.009
Marech, I., Ammendola, M., Sacco, R., Sammarco, G., Zuccalà , V., Zizzo, N., … Ranieri, G. (2016). Tumour-associated macrophages correlate with microvascular bed extension in colorectal cancer patients. Journal of Cellular and Molecular Medicine, 20(7), 1373–1380. https://doi.org/10.1111/jcmm.12826
Mazzieri, R., Pucci, F., Moi, D., Zonari, E., Ranghetti, A., Berti, A., … De Palma, M. (2011). Targeting the ANG2/TIE2 axis inhibits tumor growth and metastasis by impairing angiogenesis and disabling rebounds of proangiogenic myeloid cells. Cancer Cell, 19(4), 512–526. https://doi.org/10.1016/j.ccr.2011.02.005
McMillin, D. W., Negri, J. M., & Mitsiades, C. S. (2013). The role of tumour–stromal interactions in modifying drug response: Challenges and opportunities. Nature Reviews Drug Discovery, 12(3), 217–228. https://doi.org/10.1038/nrd3870
Meira, L. B., Bugni, J. M., Green, S. L., Lee, C.-W., Pang, B., Borenshtein, D., … Samson, L. D. (2008). DNA damage induced by chronic inflammation contributes to colon carcinogenesis in mice. The Journal of Clinical Investigation, 118(7), 2516–2525. https://doi.org/10.1172/JCI35073
Miller, K. D., Siegel, R. L., Lin, C. C., Mariotto, A. B., Kramer, J. L., Rowland, J. H., … Jemal, A. (2016). Cancer treatment and survivorship statistics, 2016. CA: A Cancer Journal for Clinicians, 66(4), 271–289. https://doi.org/10.3322/caac.21349
Movahedi, K., Laoui, D., Gysemans, C., Baeten, M., Stangé, G., Van den Bossche, J., … Van Ginderachter, J. A. (2010). Different tumor microenvironments contain functionally distinct subsets of macrophages derived from Ly6C(high) monocytes. Cancer Research, 70(14), 5728. https://doi.org/10.1158/0008-5472.CAN-09-4672
Nowak, A. K., Cook, A. M., McDonnell, A. M., Millward, M. J., Creaney, J., Francis, R. J., … Lake, R. A. (2015). A phase 1b clinical trial of the CD40-activating antibody CP-870,893 in combination with cisplatin and pemetrexed in malignant pleural mesothelioma. Annals of Oncology, 26(12), 2483–2490. https://doi.org/10.1093/annonc/mdv387
Noy, R., & Pollard, J. W. (2014). Tumor-associated macrophages: From mechanisms to therapy. Immunity, 41(1), 49–61. https://doi.org/10.1016/j.immuni.2014.06.010
Ohno, S., Inagawa, H., Dhar, D. K., Fujii, T., Ueda, S., Tachibana, M., … Nagasue, N. (2003). The degree of macrophage infiltration into the cancer cell nest is a significant predictor of survival in gastric cancer patients. Anticancer Research, 23(6D), 5015–5022.
Palaga, T., Ratanabunyong, S., Pattarakankul, T., Sangphech, N., Wongchana, W., Hadae, Y., & Kueanjinda, P. (2013). Notch signaling regulates expression of Mcl-1 and apoptosis in PPD-treated macrophages. Cellular & Molecular Immunology, 10(5), 444–452. https://doi.org/10.1038/cmi.2013.22
Pang, B., Zhou, X., Yu, H., Dong, M., Taghizadeh, K., Wishnok, J. S., … Dedon, P. C. (2007). Lipid peroxidation dominates the chemistry of DNA adduct formation in a mouse model of inflammation. Carcinogenesis, 28(8), 1807–1813. https://doi.org/10.1093/carcin/bgm037
Pedroza-Gonzalez, A., Xu, K., Wu, T.-C., Aspord, C., Tindle, S., Marches, F., … Palucka, A. K. (2011). Thymic stromal lymphopoietin fosters human breast tumor growth by promoting type 2 inflammation. The Journal of Experimental Medicine, 208(3), 479–490. https://doi.org/10.1084/jem.20102131
Pinto, M. L., Rios, E., Silva, A. C., Neves, S. C., Caires, H. R., Pinto, A. T., … Oliveira, M. J. (2017). Decellularized human colorectal cancer matrices polarize macrophages towards an anti-inflammatory phenotype promoting cancer cell invasion via CCL18. Biomaterials, 124, 211–224. https://doi.org/10.1016/j.biomaterials.2017.02.004
Porta, C., Rimoldi, M., Raes, G., Brys, L., Ghezzi, P., Di Liberto, D., … Sica, A. (2009). Tolerance and M2 (alternative) macrophage polarization are related processes orchestrated by p50 nuclear factor kappaB. Proceedings of the National Academy of Sciences of the United States of America, 106(35), 14978–14983. https://doi.org/10.1073/pnas.0809784106
Qian, B.-Z., Li, J., Zhang, H., Kitamura, T., Zhang, J., Campion, L. R., … Pollard, J. W. (2011). CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. Nature, 475(7355), 222–225. https://doi.org/10.1038/nature10138
Qian, B.-Z., & Pollard, J. W. (2010). Macrophage diversity enhances tumor progression and metastasis. Cell, 141(1), 39–51. https://doi.org/10.1016/j.cell.2010.03.014
Quail, D. F., & Joyce, J. A. (2017). Molecular pathways: Deciphering mechanisms of resistance to macrophage-targeted therapies. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 23(4), 876–884. https://doi.org/10.1158/1078-0432.CCR-16-0133
Rai, R. K., Vishvakarma, N. K., Mohapatra, T. M., & Singh, S. M. (2012). Augmented macrophage differentiation and polarization of tumor-associated macrophages towards M1 subtype in listeria-administered tumor-bearing host. Journal of Immunotherapy, 35(7), 544–554.
Robbins, C. S., Hilgendorf, I., Weber, G. F., Theurl, I., Iwamoto, Y., Figueiredo, J.-L., … Swirski, F. K. (2013). Local proliferation dominates lesional macrophage accumulation in atherosclerosis. Nature Medicine, 19(9), 1166–1172. https://doi.org/10.1038/nm.3258
Rosas, M., Davies, L. C., Giles, P. J., Liao, C.-T., Kharfan, B., Stone, T. C., … Taylor, P. R. (2014). The transcription factor Gata6 links tissue macrophage phenotype and proliferative renewal. Science (New York, N.Y.), 344(6184), 645–648. https://doi.org/10.1126/science.1251414
Saccani, A., Schioppa, T., Porta, C., Biswas, S. K., Nebuloni, M., Vago, L., … Sica, A. (2006). p50 nuclear factor-κB overexpression in tumor-associated macrophages inhibits M1 inflammatory responses and antitumor resistance. Cancer Research, 66(23), 11432. https://doi.org/10.1158/0008-5472.CAN-06-1867
Schmidt, T., Ben-Batalla, I., Schultze, A., & Loges, S. (2012). Macrophage–tumor crosstalk: Role of TAMR tyrosine kinase receptors and of their ligands. Cellular and Molecular Life Sciences, 69(9), 1391–1414. https://doi.org/10.1007/s00018-011-0863-7
Schmitz, R., Valls, A. F., Yerbes, R., von Richter, S., Kahlert, C., Loges, S., … Schmidt, T. (2016). TAM receptors Tyro3 and Mer as novel targets in colorectal cancer. Oncotarget, 7(35), 56355–56370. https://doi.org/10.18632/oncotarget.10889
Serafini, P., Borrello, I., & Bronte, V. (2006). Myeloid suppressor cells in cancer: Recruitment, phenotype, properties, and mechanisms of immune suppression. Seminars in Cancer Biology, 16(1), 53–65. https://doi.org/10.1016/j.semcancer.2005.07.005
Shand, F. H. W., Ueha, S., Otsuji, M., Koid, S. S., Shichino, S., Tsukui, T., … Matsushima, K. (2014). Tracking of intertissue migration reveals the origins of tumor-infiltrating monocytes. Proceedings of the National Academy of Sciences of the United States of America, 111(21), 7771–7776. https://doi.org/10.1073/pnas.1402914111
Shojaei, F., & Ferrara, N. (2008). Refractoriness to antivascular endothelial growth factor treatment: Role of myeloid cells. Cancer Research, 68(14), 5501. https://doi.org/10.1158/0008-5472.CAN-08-0925
Sieweke, M. H., & Allen, J. E. (2013). Beyond stem cells: Self-renewal of differentiated macrophages. Science, 342(6161), 1242974. https://doi.org/10.1126/science.1242974
Silva, V. L., & Al-Jamal, W. T. (2017). Exploiting the cancer niche: Tumor-associated macrophages and hypoxia as promising synergistic targets for nano-based therapy. Journal of Controlled Release, 253, 82–96. https://doi.org/10.1016/j.jconrel.2017.03.013
Soni, V. K., Shukla, D., Kumar, A., & Vishvakarma, N. K. (2020). Curcumin circumvent lactate-induced chemoresistance in hepatic cancer cells through modulation of Hydroxycarboxylic acid receptor-1. International Journal of Biochemistry & Cell Biology, 123, 105752. https://doi.org/10.1016/j.biocel.2020.105752
Steeg, P. S. (2006). Tumor metastasis: Mechanistic insights and clinical challenges. Nature Medicine, 12(8), 895–904. https://doi.org/10.1038/nm1469
Stitt, T. N., Conn, G., Goret, M., Lai, C., Bruno, J., Radzlejewski, C., … Yancopoulos, G. D. (1995). The anticoagulation factor protein S and its relative, Gas6, are ligands for the Tyro 3/Axl family of receptor tyrosine kinases. Cell, 80(4), 661–670. https://doi.org/10.1016/0092-8674(95)90520-0
Sugita, J., Ohtani, H., Mizoi, T., Saito, K., Shiiba, K., Sasaki, I., … Nagura, H. (2002). Close association between Fas ligand (FasL; CD95L)-positive tumor-associated macrophages and apoptotic cancer cells along invasive margin of colorectal carcinoma: A proposal on tumor-host interactions. Japanese Journal of Cancer Research: Gann, 93(3), 320–328. https://doi.org/10.1111/j.1349-7006.2002.tb02175.x
Tang, X., Mo, C., Wang, Y., Wei, D., & Xiao, H. (2013). Anti-tumour strategies aiming to target tumour-associated macrophages. Immunology, 138(2), 93–104. https://doi.org/10.1111/imm.12023
Torroella-Kouri, M., Silvera, R., Rodriguez, D., Caso, R., Shatry, A., Opiela, S., … Lopez, D. M. (2009). Identification of a subpopulation of macrophages in mammary tumor–bearing mice that are neither M1 nor M2 and are less differentiated. Cancer Research, 69(11), 4800. https://doi.org/10.1158/0008-5472.CAN-08-3427
van Dalen, F. J., van Stevendaal, M. H. M. E., Fennemann, F. L., Verdoes, M., & Ilina, O. (2018). Molecular repolarisation of tumour-associated macrophages. Molecules (Basel, Switzerland), 24(1), 9. https://doi.org/10.3390/molecules24010009
Varnum, B. C., Young, C., Elliott, G., Garcia, A., Bartley, T. D., Fridell, Y.-W., … Yamane, H. K. (1995). Axl receptor tyrosine kinase stimulated by the vitamin K-dependent protein encoded by growth-arrest-specific gene 6. Nature, 373(6515), 623–626. https://doi.org/10.1038/373623a0
Varol, C., Vallon-Eberhard, A., Elinav, E., Aychek, T., Shapira, Y., Luche, H., … Jung, S. (2009). Intestinal lamina propria dendritic cell subsets have different origin and functions. Immunity, 31(3), 502–512. https://doi.org/10.1016/j.immuni.2009.06.025
Vishvakarma, N. K., Kumar, A., Kumar, A., Kant, S., Bharti, A. C., & Singh, S. M. (2012). Myelopotentiating effect of curcumin in tumor-bearing host: Role of bone marrow resident macrophages. Toxicology and Applied Pharmacology, 263(1), 111–121. https://doi.org/10.1016/j.taap.2012.06.004
Vishvakarma, N. K., Kumar, A., & Singh, S. M. (2011). Role of curcumin-dependent modulation of tumor microenvironment of a murine T cell lymphoma in altered regulation of tumor cell survival. Toxicology and Applied Pharmacology, 252(3), 298–306. https://doi.org/10.1016/j.taap.2011.03.002
Vishvakarma, N. K., & Singh, S. M. (2010). Immunopotentiating effect of proton pump inhibitor pantoprazole in a lymphoma-bearing murine host: Implication in antitumor activation of tumor-associated macrophages. Immunology Letters, 134(1), 83–92. https://doi.org/10.1016/j.imlet.2010.09.002
Vishvakarma, N. K., & Singh, S. M. (2011). Augmentation of myelopoiesis in a murine host bearing a T cell lymphoma following in vivo administration of proton pump inhibitor pantoprazole. Biochimie, 93(10), 1786–1796. https://doi.org/10.1016/j.biochi.2011.06.022
Wang, Y.-C., He, F., Feng, F., Liu, X.-W., Dong, G.-Y., Qin, H.-Y., … Han, H. (2010). Notch signaling determines the M1 versus M2 polarization of macrophages in antitumor immune responses. Cancer Research, 70(12), 4840. https://doi.org/10.1158/0008-5472.CAN-10-0269
Wei, S., Nandi, S., Chitu, V., Yeung, Y.-G., Yu, W., Huang, M., … Stanley, E. R. (2010). Functional overlap but differential expression of CSF-1 and IL-34 in their CSF-1 receptor-mediated regulation of myeloid cells. Journal of Leukocyte Biology, 88(3), 495–505. https://doi.org/10.1189/jlb.1209822
Yahaya, M. A. F., Lila, M. A. M., Ismail, S., Zainol, M., & Afizan, N. A. R. N. M. (2019). Tumour-associated macrophages (TAMs) in colon cancer and how to reeducate them. Journal of Immunology Research, 2019, 2368249–2368249. https://doi.org/10.1155/2019/2368249
Yamada, K., Uchiyama, A., Uehara, A., Perera, B., Ogino, S., Yokoyama, Y., … Motegi, S.-I. (2016). MFG-E8 drives melanoma growth by stimulating mesenchymal stromal cell-induced angiogenesis and M2 polarization of tumor-associated macrophages. Cancer Research, 76(14), 4283–4292. https://doi.org/10.1158/0008-5472.CAN-15-2812
Yang, H., Shao, R., Huang, H., Wang, X., Rong, Z., & Lin, Y. (2019). Engineering macrophages to phagocytose cancer cells by blocking the CD47/SIRPɑ axis. Cancer Medicine, 8(9), 4245–4253. https://doi.org/10.1002/cam4.2332
Yang, L., DeBusk, L. M., Fukuda, K., Fingleton, B., Green-Jarvis, B., Shyr, Y., … Lin, P. C. (2004). Expansion of myeloid immune suppressor Gr+CD11b+ cells in tumor-bearing host directly promotes tumor angiogenesis. Cancer Cell, 6(4), 409–421. https://doi.org/10.1016/j.ccr.2004.08.031
Yang, L., Huang, J., Ren, X., Gorska, A. E., Chytil, A., Aakre, M., … Moses, H. L. (2008). Abrogation of TGF beta signaling in mammary carcinomas recruits Gr-1+CD11b+ myeloid cells that promote metastasis. Cancer Cell, 13(1), 23–35. https://doi.org/10.1016/j.ccr.2007.12.004
Yang, L., & Zhang, Y. (2017). Tumor-associated macrophages: From basic research to clinical application. Journal of Hematology & Oncology, 10(1), 58. https://doi.org/10.1186/s13045-017-0430-2
Yin, Y., Yao, S., Hu, Y., Feng, Y., Li, M., Bian, Z., … Huang, Z. (2017). The immune-microenvironment confers chemoresistance of colorectal cancer through macrophage-derived IL6. Clinical Cancer Research, 23(23), 7375. https://doi.org/10.1158/1078-0432.CCR-17-1283
Zhong, X., Chen, B., & Yang, Z. (2018). The role of tumor-associated macrophages in colorectal carcinoma progression. Cellular Physiology and Biochemistry, 45(1), 356–365. https://doi.org/10.1159/000486816
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2022 The Author(s), under exclusive license to Springer Nature Switzerland AG
About this chapter
Cite this chapter
Mehta, A. et al. (2022). Role of Tumour-Associated Macrophages in Colon Cancer Progression and Its Therapeutic Targeting. In: Shukla, D., Vishvakarma, N.K., Nagaraju, G.P. (eds) Colon Cancer Diagnosis and Therapy Vol. 3. Springer, Cham. https://doi.org/10.1007/978-3-030-72702-4_10
Download citation
DOI: https://doi.org/10.1007/978-3-030-72702-4_10
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-72701-7
Online ISBN: 978-3-030-72702-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)