Abstract
Cancer immunology is among the most important disciplines of cellular and molecular immunology, and it has progressed significantly in the last decade. A tumor is a mass of tissue that develops as a result of uncontrolled cell division. The ability of tumor cells to proliferate and invade distant areas is the key feature of tumor cells. In this regard, the immune system plays an important role in the suppression or progression of tumor growth. The immune microenvironment around the tumor consists of a heterogeneous population of immune cells with specific roles. Some of them, such as myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), and M2 macrophages, through the expression of immunosuppressive molecules, could exert a protumor role, leading to cancer progression. In contrast, several types of immune cells, such as cytotoxic T lymphocytes (CTL) and natural killer cells (NK), fight against tumor development by exerting antitumor mechanisms. Therefore, understanding the function of immune system arms might help in determining antitumor responses or even therapeutic options. This chapter provides an overview of the immune system’s role, as well as key immune system players in the tumor microenvironment. It also provides some of the most common immune-based therapies.
Similar content being viewed by others
References
Acuff HB, Carter KJ, Fingleton B, Gorden DL, Matrisian LM (2006) Matrix metalloproteinase-9 from bone marrow-derived cells contributes to survival but not growth of tumor cells in the lung microenvironment. Cancer Res 66:259–266
Balkwill F, Mantovani A (2001) Inflammation and cancer: back to virchow? Lancet 357:539–545
Beatty GL, Gladney WL (2015) Immune escape mechanisms as a guide for cancer immunotherapy. Clin Cancer Res 21:687–692. https://doi.org/10.1158/1078-0432.CCR-14-1860
Binnewies M, Roberts EW, Kersten K, Chan V, Fearon DF, Merad M et al (2018) Understanding the tumor immune microenvironment (TIME) for effective therapy. Nat Med 24:541–550
Blankenstein T, Coulie PG, Gilboa E, Jaffee EM (2012) The determinants of tumour immunogenicity. Nat Rev Cancer 12:307–313. https://doi.org/10.1038/nrc3246
Burnet M (1957) Cancer: a biological approach. III. Viruses associated with neoplastic conditions. IV. Practical applications. Br Med J 1:841–847
Cantley LC, Neel BG (1999) New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway. Proc Natl Acad Sci U S A 96:4240–4245
Coley WB (1991) The treatment of malignant tumors by repeated inoculations of erysipelas. With a report of ten original cases 1893. Clin Orthop 262:3–11
Condamine T, Ramachandran I, Youn JI, Gabrilovich DI (2015) Regulation of tumor metastasis by myeloid-derived suppressor cells. Annu Rev Med 66:97–110
Constant SL, Bottomly K (1997) Induction of Th1 and Th2 CD4+ T cell responses: the alternative approaches. Annu Rev Immunol 15:297–322
Cools-Lartigue J, Spicer J, McDonald B, Gowing S, Chow S, Giannias B et al (2013) Neutrophil extracellular traps sequester circulating tumor cells and promote metastasis. J Clin Invest 123:3446–3458
Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A et al (2004) Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. New Eng J Med 351:337–345
Dighe AS, Richards E, Old LJ, Schreiber RD (1994) Enhanced in vivo growth and resistance to rejection of tumor cells expressing dominant negative IFNγ receptors. Immunity 1:447–456
Downward J (1998) Mechanisms and consequences of activation of protein kinase B/Akt. Curr Opin Cell Biol 10:262–267
Ehrlich P (1909) Uber den jetzigen Stand der Karzinomforschung. Ned Tijdschr Genees 5:273–290
Esfahani K, Roudaia L, Buhlaiga N, Del Rincon SV, Papneja N, Miller WH Jr (2020) A review of cancer immunotherapy: from the past, to the present, to the future. Curr Oncol 27:S87–S97. https://doi.org/10.3747/co.27.5223
Evan G, Littlewood T (1998) A matter of life and cell death. Science 281:1317–1322
Fedi P, Tronick SR, Aaronson SA (1997) Growth factors. In: Holland JF, Bast RC, Morton DL, Frei E, Kufe DW, Weichselbaum RR (eds) Cancer medicine. Williams and Wilkins, Baltimore, MD, pp 41–64
Fouad YA, Aanei C (2017) Revisiting the hallmarks of cancer. Am J Cancer Res 7:1016–1036
Fricke I, Gabrilovich DI (2006) Dendritic cells and tumor microenvironment: a dangerous liaison. Immunol Investig 35:459–483. https://doi.org/10.1080/08820130600803429
Gattinoni L, Powell DJ Jr, Rosenberg SA, Restifo NP (2006) Adoptive immunotherapy for cancer: building on success. Nat Rev Immunol 6:383–393. https://doi.org/10.1038/nri1842
Gershon RK, Kondo K (1970) Cell interactions in the induction of tolerance: the role of thymic lymphocytes. Immunology 18:723–737
Gershon RK, Kondo K (1971) Infectious immunological tolerance. Immunology 21:903–914
Ghajar CM, Bissell MJ (2008) Extracellular matrix control of mammary gland morphogenesis and tumorigenesis: insights from imaging. Histochem Cell Biol 130:1105–1118
Gocheva V, Wang HW, Gadea BB, Shree T, Hunter KE, Garfall AL et al (2010) IL-4 induces cathepsin protease activity in tumor-associated macrophages to promote cancer growth and invasion. Genes Dev 24:241–255
Goldenberg MM (1999) Trastuzumab, a recombinant DNA-derived humanized monoclonal antibody, a novel agent for the treatment of metastatic breast cancer. Clin Ther 21:309–318
Graham C, Hewitson R, Pagliuca A, Benjamin R (2018) Cancer immunotherapy with CAR-T cells-behold the future. Clin Med (Lond) 18:324–328. https://doi.org/10.7861/clinmedicine.18-4-324
Griesser H, Mak TW (1994) The T-cell receptor–structure, function, and clinical application. Hematol Pathol 8:1–23
Grillo-Lopez AJ, White CA, Dallaire BK, Varns CL, Shen CD, Wei A et al (2000) Rituximab: the first monoclonal antibody approved for the treatment of lymphoma. Curr Pharm Biotechnol 1:1–9
Groux H, O'Garra A, Bigler M, Rouleau M, Antonenko S, de Vries JE et al (1997) A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature 389:737–742
Gumperz JE, Miyake S, Yamamura T, Brenner MB (2002) Functionally distinct subsets of CD1d-restricted natural killer T cells revealed by CD1d tetramer staining. J Exp Med 195:625–636. https://doi.org/10.1084/jem.20011786
Gutschner T, Diederichs S (2012) The hallmarks of cancer: a long non-coding RNA point of view. RNA Biol 9:703–719. https://doi.org/10.4161/rna.20481
Harris CC (1996) p53 tumor suppressor gene: from the basic research laboratory to the clinic—an abridged historical perspective. Carcinogenesis 17:1187–1198
Henkart PA (1997) CTL effector functions. Semin Immunol 9:85–86
Hor JL, Whitney PG, Zaid A, Brooks AG, Heath WR, Mueller SN (2015) Spatiotemporally distinct interactions with dendritic cell subsets facilitates cd4+ and cd8+ t cell activation to localized viral infection. Immunity 43:554–565
Hoshino A, Costa-Silva B, Shen TL, Rodrigues G, Hashimoto A, Tesic Mark M et al (2015) Tumour exosome integrins determine organotropic metastasis. Nature 527:329–335
Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W et al (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. New Eng J Med 350:2335–2342
Jia L, Wu C (2014) The biology and functions of Th22 cells. Adv Exp Med Biol 841:209–230
Kennedy R, Celis E (2008) Multiple roles for CD4+ T cells in anti-tumor immune responses. Immunol Rev 222:129–144
Kim JH, Kim BS, Lee SK (2020) Regulatory T cells in tumor microenvironment and approach for anticancer immunotherapy. Immune Netw 20:e4. https://doi.org/10.4110/in.2020.20.e4
Kinjo Y, Illarionov P, Vela JL, Pei B, Girardi E, Li X et al (2011) Invariant natural killer T cells recognize glycolipids from pathogenic Gram-positive bacteria. Nat Immunol 12:966–974. https://doi.org/10.1038/ni.2096
Kosmaczewska A, Ciszak L, Boćko D, Frydecka I (2001) Expression and functional significance of CTLA-4, a negative regulator of T cell activation. Arch Immunol Ther Exp 49:39–46
Krasnova Y, Putz EM, Smyth MJ, Souza-Fonseca-Guimaraes F (2017) Bench to bedside: NK cells and control of metastasis. Clin Immunol 177:50–59
Krijgsman D, Hokland M, Kuppen PJK (2018) The role of natural killer T cells in cancer-a phenotypical and functional approach. Front Immunol 9:367. Published 2018 Feb 27. https://doi.org/10.3389/fimmu.2018.00367
Kumar V, Patel S, Tcyganov E, Gabrilovich DI (2016) The nature of myeloid-derived suppressor cells in the tumor microenvironment. Trends Immunol 37:208–220. https://doi.org/10.1016/j.it.2016.01.004
Kumar V, Delovitch TL (2014) Different subsets of natural killer T cells may vary in their roles in health and disease. Immunology 142:321–336. https://doi.org/10.1111/imm.12247
Larsen SK, Gao Y, Basse PH (2014) NK cells in the tumor microenvironment. Crit Rev Oncog 19:91–105. https://doi.org/10.1615/critrevoncog.2014011142
Levine AJ (1997) p53, the cellular gatekeeper for growth and division. Cell 88:323–331
Li T, Wu B, Yang T, Zhang L, Jin K (2020a) The outstanding antitumor capacity of CD4+ T helper lymphocytes. Biochim Biophys Acta Rev Cancer 1874:188439
Li C, Jiang P, Wei S, Xu X, Wang J (2020b) Regulatory T cells in tumor microenvironment: new mechanisms, potential therapeutic strategies and future prospects. Mol Cancer 19:116
Linke R, Klein A, Seimetz D (2010) Catumaxomab: clinical development and future directions. MAbs 2:129–136. https://doi.org/10.4161/mabs.2.2.11221
Liu Y, Cao X (2016) Characteristics and significance of the pre-metastatic niche. Cancer Cell 30:668–681
Liu M, Guo F (2018) Recent updates on cancer immunotherapy. Precis Clin Med 1:65–74. https://doi.org/10.1093/pcmedi/pby011
Lonial S, Dimopoulos M, Palumbo A, White D, Grosicki S, Spicka I et al (2015) Elotuzumab therapy for relapsed or refractory multiple myeloma. N Engl J Med 373:621–631
Ma Y, Shurin GV, Peiyuan Z, Shurin MR (2013) Dendritic cells in the cancer microenvironment. J Cancer 4:36–44. https://doi.org/10.7150/jca.5046
Maddur MS, Miossec P, Kaveri SV, Bayry J (2012) Th17 cells: biology, pathogenesis of autoimmune and inflammatory diseases, and therapeutic strategies. Am J Pathol 181:8–18
Maimela NR, Liu S, Zhang Y (2019) Fates of CD8+ T cells in tumor microenvironment. Comput Struct Biotechnol J 17:1–13
Mark JS, Gavin PD, Robert DS (2006) Cancer immunosurveillance and immunoediting: the roles of immunity in suppressing tumor development and shaping tumor immunogenicity. Adv Immunol 90:1–50
Marzo AL, Kinnear BF, Lake RA, Frelinger JJ, Collins EJ, Robinson BW et al (2000) Tumor-specific CD4+ T cells have a major “post-licensing” role in CTL mediated anti-tumor immunity. J Immunol 165:6047–6055
Medawar P (1944) The behaviour and fate of skin autografts and skin homografts in rabbits. J Anat 78:176–199
Moller G (1988) Do suppressor T cells exist? Scand J Immunol 27:247–250
Mukherji B, Chakraborty NG, Sivanandham M (1990) T-cell clones that react against autologous human tumors. Immunol Rev 116:33–62
Müller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME et al (2001) Involvement of chemokine receptors in breast cancer metastasis. Nature 410:50–56
Noy R, Pollard JW (2014) Tumor-associated macrophages: from mechanisms to therapy. Immunity 41:49–61. https://doi.org/10.1016/j.immuni.2014.06.010
Offner S, Hofmeister R, Romaniuk A, Kufer P, Baeuerle PA (2006) Induction of regular cytolytic T cell synapses by bispecific single-chain antibody constructs on MHC class I-negative tumor cells. Mol Immunol 43:763–771. https://doi.org/10.1016/j.molimm.2005.03.007
Oliphant CJ, Barlow JL, Mckenzie AN (2011) Insights into the initiation of type 2 immune responses. Immunol 134:378–385
Ossendorp F et al (1998) Specific T helper cell requirement for optimal induction of cytotoxic T lymphocytes against major histocompatibility complex class II negative tumors. J Exp Med 187:693–702
Pagès F, Kirilovsky A, Mlecnik B, Asslaber M, Tosolini M, Bindea G et al (2009) In situ cytotoxic and memory T cells predict outcome in patients with early-stage colorectal cancer. J Clin Oncol 2:5944–5951
Paget S (1889) The distribution of secondary growths in cancer of the breast. Lancet 133:571–573
Pan Y, Yu Y, Wang X, Zhang T (2021) Tumor-associated macrophages in tumor immunity. Front Immunol 12:775758. https://doi.org/10.3389/fimmu.2020.583084
Parker CM, Groh V, Band H, Porcelli SA, Morita C, Fabbi M et al (1990) Evidence for extrathymic changes in the T cell receptor gamma/delta repertoire. J Exp Med 171:1597–1612
Paul S, Lal G (2017) The molecular mechanism of natural killer cells function and its importance in cancer immunotherapy. Front Immunol 8:1124
Peinado H, Alečković M, Lavotshkin S, Matei I, Costa-Silva B, Moreno-Bueno G et al (2012) Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat Med 18:883–891
Lo Presti E, Pizzolato G, Corsale AM, Caccamo N, Sireci G, Dieli F et al (2018) γδ T cells and tumor microenvironment: from immunosurveillance to tumor evasion. Front Immunol 9:1395. https://doi.org/10.3389/fimmu.2018.01395
Pugh CW, Ratcliffe PJ (2003) Regulation of angiogenesis by hypoxia: role of the HIF system. Nat Med 9:677–684
Romagnani S (1991) Type 1 T helper and type 2 T helper cells: functions, regulation and role in protection and disease. Int J Clin Lab Res 21:152–158
Sakaguchi S, Miyara M, Costantino CM, Hafler DA (2010) FOXP3+ regulatory T cells in the human immune system. Nat Rev Immunol 10:490–500
Saxena M, van der Burg SH, Melief CJM, Bhardwaj N et al (2021) Therapeutic cancer vaccines. Nat Rev Cancer 21:360–378
Sedykh SE, Prinz VV, Buneva VN, Nevinsky GA (2018) Bispecific antibodies: design, therapy, perspectives. Drug Des Devel Ther 12:195–208. https://doi.org/10.2147/DDDT.S151282
Sharonov GV, Serebrovskaya EO, Yuzhakova DV, Britanova OV, Chudakov DM et al (2020) B cells, plasma cells and antibody repertoires in the tumour microenvironment. Nat Rev Immunol 20:294–307
Shedlock DJ, Shen H (2003) Requirement for CD4 T cell help in generating functional CD8 T cell memory. Science 300(5617):337
Slaney CY, Kershaw MH, Darcy PK (2014) Trafficking of T cells into tumors. Cancer Res 74:7168
De Sousa JR, Quaresma J (2018) The role of T helper 25 cells in the immune response to Mycobacterium leprae. J Am Acad Dermatol 78:1009–1011
Spicer JD, McDonald B, Cools-Lartigue JJ, Chow SC, Giannias B, Kubes P et al (2012) Neutrophils promote liver metastasis via Mac-1-mediated interactions with circulating tumor cells. Cancer Res 72:3919–3927
Stanton SE, Disis ML (2016) Clinical significance of tumor-infiltrating lymphocytes in breast cancer. J Immunother Cancer 4:59
Sullivan JA, Tomita Y, Jankowska-Gan E, Lema DA, Arvedson MP, Nair A et al (2020) Treg-cell-derived IL-35-coated extracellular vesicles promote infectious tolerance. Cell Rep 30:1039–51 e1035
Tan W, Zhang W, Strasner A, Grivennikov S, Cheng JQ, Hoffman M, Karin M (2011) Fibroblast-recruited, tumor-infiltrating CD4+ T cells stimulate mammary cancer metastasis through RANKL-RANK signaling. Nature 470:548–553
Thomas L (1959) Discussion. In: Lawrence HS (ed) Cellular and humoral aspects of the hypersensitive states. Hoeber-Harper, New York, pp 529–532
Usmani S, Weiss BM, Plesner T, Bahlis NJ, Belch A, Lonial S et al (2015) Clinical efficacy of daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma. Blood 126:29–29
Veglia F, Perego M, Gabrilovich D (2018) Myeloid-derived suppressor cells coming of age. Nat Immunol 19:108–119. https://doi.org/10.1038/s41590-017-0022-x
Veikkola T, Alitalo K (1999) VEGFs, receptors and angiogenesis. Semin Cancer Biol 9:211–220
Vivier E, Tomasello E, Baratin M, Walzer T, Ugolini S (2008) Functions of natural killer cells. Nat Immunol 9:503–510
Wherry EJ, Kurachi M (2015) Molecular and cellular insights into T cell exhaustion. Nat Rev Immunol 15:486–499
Wu SY, Fu T, Jiang YZ, Shao ZM (2020) Natural killer cells in cancer biology and therapy. Mol Cancer 19:120
Wyckoff J, Wang W, Lin EY, Wang Y, Pixley F, Stanley ER et al (2004) A paracrine loop between tumor cells and macrophages is required for tumor cell migration in mammary tumors. Cancer Res 64:7022–7029
Zhou D, Mattner J, Cantu C III, Schrantz N, Yin N, Gao Y et al (2004) Lysosomal glycosphingolipid recognition by NKT cells. Science 306:1786–1789. https://doi.org/10.1126/science.1103440
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2023 Springer Nature Switzerland AG
About this entry
Cite this entry
Sadeghalvad, M., Mohammadi-Motlagh, HR., Rezaei, N. (2023). Introduction to Cancer Immunology. In: Rezaei, N. (eds) Handbook of Cancer and Immunology. Springer, Cham. https://doi.org/10.1007/978-3-030-80962-1_1-1
Download citation
DOI: https://doi.org/10.1007/978-3-030-80962-1_1-1
Received:
Accepted:
Published:
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