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Role of Immune Cells in the Tumor Microenvironment

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Handbook of Cancer and Immunology

Abstract

Immune cells of different lineages in the tumor microenvironment (TME) play essential roles in tumorigenesis. Some cells act against the tumor, while others show tumor-supporting functions. During early tumorigenesis, cells with anti-tumor activity attempt to target and kill the cancer cells.. However, through evasion of immune surveillance and/or inhibition of immune cell cytotoxicity, cancer cells are able to escape cell death. Paradoxically, this immune evasion capacity provides an opportunity for research and development of new cancer therapy strategies, thus taking advantage of the characteristics and capabilities of immune cells to attack cancer cells.

The principal intention of this chapter is to give the reader a synopsis of the immune cell biological functions within the TME and discuss their influence in cancer immunotherapy and outline prospects of future research that will contribute to more insight into the functions of immune cells that would open new opportunities for future therapies. An example of this is the use of therapies that block immune checkpoints (anti-CTLA4, anti-LAG3, and anti-PD antibodies) or direct immune cells (CAR-T). These anti-cancer therapies have shown significant anti-tumor effects in multiple cancers, thus ushering in a new era in cancer therapy.

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References

  • Cerwenka A, Lanier LL (2016) Natural killer cell memory in infection, inflammation and cancer. Nat Rev Immunol 16(2):112–123

    Article  CAS  PubMed  Google Scholar 

  • Chevrier S, Levine JH, Zanotelli VRT, Silina K et al (2017) An Immune atlas of clear cell renal cell carcinoma. Cell 169(4):736–749.e718

    Article  Google Scholar 

  • Chun E, Lavoie S, Michaud M, Gallini CA et al (2015) CCL2 promotes colorectal carcinogenesis by enhancing polymorphonuclear myeloid-derived suppressor cell population and function. Cell Rep 12(2):244–257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cursons J, Souza-Fonseca-Guimaraes F, Foroutan M, Anderson A et al (2019) A gene signature predicting natural killer cell infiltration and improved survival in melanoma patients. Cancer Immunol Res 7(7):1162–1174

    Article  CAS  PubMed  Google Scholar 

  • Da Gama Duarte J, Peyper JM, Blackburn JM (2018) B cells and antibody production in melanoma. Mamm Genome 29(11-12):790–805

    Article  PubMed  Google Scholar 

  • Derakhshani A, Vahidian F, Alihasanzadeh M, Mokhtarzadeh A et al (2019) Mast cells: a double-edged sword in cancer. Immunol Lett 209:28–35

    Article  CAS  PubMed  Google Scholar 

  • Engblom C, Pfirschke C, Pittet MJ (2016) The role of myeloid cells in cancer therapies. Nat Rev Cancer 16(7):447–462

    Article  CAS  PubMed  Google Scholar 

  • Frossi B, Mion F, Sibilano R, Danelli L, Pucillo CEM (2018) Is it time for a new classification of mast cells? What do we know about mast cell heterogeneity? Immunol Rev 282(1):35–46

    Article  CAS  PubMed  Google Scholar 

  • Gao S, Hsu T-W, Li MO (2021) Immunity beyond cancer cells: perspective from tumor tissue. Trends Cancer 7(11):1010–1019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hanna RN, Cekic C, Sag D, Tacke R et al (2015) Patrolling monocytes control tumor metastasis to the lung. Science 350(6263):985–990

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Headley MB, Bins A, Nip A, Roberts EW et al (2016) Visualization of immediate immune responses to pioneer metastatic cells in the lung. Nature 531(7595):513–517

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jeong H-J, Oh H-A, Nam S-Y, Han N-R et al (2013) The critical role of mast cell-derived hypoxia-inducible factor-1α in human and mice melanoma growth. Int J Cancer 132(11):2492–2501

    Article  CAS  PubMed  Google Scholar 

  • Lavin Y, Mortha A, Rahman A, Merad M (2015) Regulation of macrophage development and function in peripheral tissues. Nat Rev Immunol 15(12):731–744

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li H, Xiao Y, Li Q, Yao J et al (2021) The allergy mediator histamine confers resistance to immunotherapy in cancer patients via activation of the macrophage histamine receptor H1. Cancer Cell

    Google Scholar 

  • Lu L, Weng C, Mao H, Fang X et al (2016) IL-17A promotes migration and tumor killing capability of B cells in esophageal squamous cell carcinoma. Oncotarget 7(16):21853–21864

    Article  PubMed  PubMed Central  Google Scholar 

  • Nielsen JS, Sahota RA, Milne K, Kost SE et al (2012) CD20+ tumor-infiltrating lymphocytes have an atypical CD27− memory phenotype and together with CD8+ T cells promote favorable prognosis in ovarian cancer. Clin Cancer Res 18(12):3281–3292

    Article  CAS  PubMed  Google Scholar 

  • Noto CN, Hoft SG, DiPaolo RJ (2021) Mast cells as important regulators in autoimmunity and cancer development. Front Cell Dev Biol 9:752350

    Article  PubMed  PubMed Central  Google Scholar 

  • Noy, R. and W. Pollard, Jeffrey (2014). Tumor-associated macrophages: from mechanisms to therapy. Immunity 41(1): 49-61.

    Google Scholar 

  • Qian B-Z, Li J, Zhang H, Kitamura T et al (2011) CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. Nature 475(7355):222–225

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Raskov H, Orhan A, Christensen JP, Gögenur I (2021) Cytotoxic CD8+ T cells in cancer and cancer immunotherapy. Br J Cancer 124(2):359–367

    Article  CAS  PubMed  Google Scholar 

  • Riabov V, Gudima A, Wang N, Mickley A et al (2014) Role of tumor associated macrophages in tumor angiogenesis and lymphangiogenesis. Front Physiol 5:75

    Article  PubMed  PubMed Central  Google Scholar 

  • Shen M, Wang J, Yu W, Zhang C et al (2018) A novel MDSC-induced PD-1−PD-L1+ B-cell subset in breast tumor microenvironment possesses immuno-suppressive properties. OncoImmunology 7(4):e1413520

    Article  PubMed  PubMed Central  Google Scholar 

  • Somasundaram R, Zhang G, Fukunaga-Kalabis M, Perego M et al (2017) Tumor-associated B-cells induce tumor heterogeneity and therapy resistance. Nat Commun 8(1)

    Google Scholar 

  • Somasundaram R, Connelly T, Choi R, Choi H et al (2021) Tumor-infiltrating mast cells are associated with resistance to anti-PD-1 therapy. Nat Commun 12(1):346

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tao H, Lu L, Xia Y, Dai F et al (2015) Antitumor effector B cells directly kill tumor cells via the Fas/FasL pathway and are regulated by IL-10. Eur J Immunol 45(4):999–1009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Theurich S, Schlaak M, Steguweit H, Heukamp LC et al (2016) Targeting tumor-infiltrating B cells in cutaneous T-cell lymphoma. J Clin Oncol 34(12):e110–e116

    Article  CAS  PubMed  Google Scholar 

  • Ugel S, Canè S, De Sanctis F, Bronte V (2021) Monocytes in the tumor microenvironment. Annu Rev Pathol Mech Dis 16(1):93–122

    Article  CAS  Google Scholar 

  • Wang Y, Schafer CC, Hough KP, Tousif S et al (2018) Myeloid-derived suppressor cells impair B cell responses in lung cancer through IL-7 and STAT5. J Immunol 201(1):278–295

    Article  CAS  PubMed  Google Scholar 

  • Winkler JK, Schiller M, Bender C, Enk AH, Hassel JC (2018) Rituximab as a therapeutic option for patients with advanced melanoma. Cancer Immunol Immunother 67(6):917–924

    Article  CAS  PubMed  Google Scholar 

  • Yu J, Xu Z, Guo J, Yang K et al (2021) Tumor-associated macrophages (TAMs) depend on MMP1 for their cancer-promoting role. Cell Death Dis 7(1)

    Google Scholar 

  • Yuen GJ, Demissie E, Pillai S (2016) B lymphocytes and cancer: a love–hate relationship. Trends Cancer 2(12):747–757

    Article  PubMed  PubMed Central  Google Scholar 

  • Zheng X, Qian Y, Fu B, Jiao D et al (2019) Mitochondrial fragmentation limits NK cell-based tumor immunosurveillance. Nat Immunol 20(12):1656–1667

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

Studies from the laboratory were supported by NIH grants RO1CA238237, PO1CA114046, and P50CA174523 and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation.

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Correspondence to Meenhard Herlyn .

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Ramirez-Salazar, E., Schenck, S., Herlyn, M. (2023). Role of Immune Cells in the Tumor Microenvironment. In: Rezaei, N. (eds) Handbook of Cancer and Immunology. Springer, Cham. https://doi.org/10.1007/978-3-030-80962-1_84-1

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  • DOI: https://doi.org/10.1007/978-3-030-80962-1_84-1

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  • Print ISBN: 978-3-030-80962-1

  • Online ISBN: 978-3-030-80962-1

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