Cancer immunology

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Cancer immunology is an interdisciplinary branch of biology that is concerned with understanding the role of the immune system in the progression and development of cancer; the most well known application is cancer immunotherapy, which utilises the immune system as a treatment for cancer. Cancer immunosurveillance and immunoediting are based on protection against development of tumors in animal systems and (ii) identification of targets for immune recognition of human cancer.

Definition[edit]

Cancer immunology is an interdisciplinary branch of biology concerned with the role of the immune system in the progression and development of cancer; the most well known application is cancer immunotherapy, where the immune system is used to treat cancer.[1][2] Cancer immunosurveillance is a theory formulated in 1957 by Burnet and Thomas, who proposed that lymphocytes act as sentinels in recognizing and eliminating continuously arising, nascent transformed cells.[3][4] Cancer immunosurveillance appears to be an important host protection process that decreases cancer rates through inhibition of carcinogenesis and maintaining of regular cellular homeostasis.[5] It has also been suggested that immunosurveillance primarily functions as a component of a more general process of cancer immunoediting.[3]

Tumor antigens[edit]

Tumors may express tumor antigens that are recognized by the immune system and may induce an immune response.[6] These tumor antigens are either TSA (Tumor-specific antigen) or TAA (Tumor-associated antigen).[7]

Tumor-specific antigens are antigens that only occur in tumor cells.[7] TSAs can be products of oncoviruses like E6 and E7 proteins of Human papillomavirus, occurring in cervical carcinoma, or EBNA-1 protein of EBV, occurring in Burkitt’s lymphoma cells. [8][9] Another example of TSAs are abnormal products of mutated oncogenes (e.g. ras) and anti-oncogenes (e.g. p53). [10]

Tumor-associated antigens are present in healthy cells, but for some reason they also occur in tumor cells. [7] However, they differ in quantity, place or time period of expression.[11] Oncofetal antigens are tumor-associated antigens expressed by embryonic cells and by tumors.[12] Examples of oncofetal antigens are AFP (α-fetoprotein), produced by hepatocellular carcinoma, or CEA (carcinoembryonic antigen), occurring in ovarian and colon cancer.[13][14] More tumor-associated antigens are HER2/neu, EGFR or MAGE-1.[15][16][17]

Cancer immunoediting[edit]

Cancer immunoediting is a process in which immune system interacts with tumor cells. It consists of three phases: elimination, equilibrium and escape. These phases are often referred to as "the three Es" of cancer immunoediting. Both, adaptive and innate immune system participate in immunoediting.[18]

In the elimination phase, the immune response leads to destruction of tumor cells and therefore to tumor suppression. However, some tumor cells may gain more mutations, change their characteristics and evade the immune system. These cells might enter the equilibrium phase, in which the immune system doesn’t recognise all tumor cells, but at the same time the tumor doesn’t grow. This condition may lead to the phase of escape, in which the tumor gains dominance over immune system, starts growing and establishes immunosuppressive environment. [19]

As a consequence of immunoediting, tumor cell clones less responsive to the immune system gain dominance in the tumor through time, as the recognized cells are eliminated. Therefore the tumor consist of cells with decreased immunogenicity and can hardly be eliminated.[19] This phenomenon was proven to happen as a result of immunotherapies of cancer patients.[20]

Mechanisms of tumor evasion from the immune response[edit]

Tumor cells have developed various mechanisms to escape immune surveillance.  

CD8+ cytotoxic T cells are a fundamental element of anti-tumor immunity. Their TCR receptors recognise antigens presented by MHC class I and when bound, the Tc cell triggers its cytotoxic activity. MHC I are present on the surface of all nucleated cells. However, some cancer cells lower their MHC I expression and avoid being detected by the cytotoxic T cells.[21] This can be done by mutation of MHC I gene, or by lowering the sensitivity to IFN-γ (which influences the surface expression of MHC I).[21][22] On the other hand, a complete loss of MHC I is a trigger for NK cells. Tumor cells therefore maintain a low expression of MHC I.[21] Another way to escape cytotoxic T cells is to stop expressing molecules essential for co-stimulation of cytotoxic T cells, such as CD80 or CD86.[23][24]

By expressing FasL on its surface, tumor calls may induce apoptosis of T lymphocytes by FasL-Fas interaction.[25]

Moreover, tumor cells may induce production of regulatory T cells by a contact dependent or independent stimulation. In a healthy tissue, functioning Tregs are essential to maintain self-tolerance. In a tumor, however, Tregs form an immunosupresive microenviroment.[26]

Cancer immunology and chemotherapy[edit]

Obeid et al.[27] investigated how inducing immunogenic cancer cell death ought to become a priority of cancer chemotherapy. He reasoned, the immune system would be able to play a factor via a ‘bystander effect’ in eradicating chemotherapy-resistant cancer cells.[28][29][30][2] However, extensive research is still needed on how the immune response is triggered against dying tumour cells.[2][31]

Professionals in the field have hypothesized that ‘apoptotic cell death is poorly immunogenic whereas necrotic cell death is truly immunogenic’.[32][33][34] This is perhaps because cancer cells being eradicated via a necrotic cell death pathway induce an immune response by triggering dendritic cells to mature, due to inflammatory response stimulation.[35][36] On the other hand, apoptosis is connected to slight alterations within the plasma membrane causing the dying cells to be attractive to phagocytic cells.[37] However, numerous animal studies have shown the superiority of vaccination with apoptotic cells, compared to necrotic cells, in eliciting anti-tumor immune responses.[38][39][40][41][42]

Thus Obeid et al.[27] propose that the way in which cancer cells die during chemotherapy is vital. Anthracyclins produce a beneficial immunogenic environment. The researchers report that when killing cancer cells with this agent uptake and presentation by antigen presenting dendritic cells is encouraged, thus allowing a T-cell response which can shrink tumours. Therefore, activating tumour-killing T-cells is crucial for immunotherapy success.[2][43]

However, advanced cancer patients with immunosuppression have left researchers in a dilemma as to how to activate their T-cells. The way the host dendritic cells react and uptake tumour antigens to present to CD4+ and CD8+ T-cells is the key to success of the treatment.[2][44]

See also[edit]

References[edit]

  1. ^ Miller JF, Sadelain M (April 2015). "The journey from discoveries in fundamental immunology to cancer immunotherapy". Cancer Cell. 27 (4): 439–49. doi:10.1016/j.ccell.2015.03.007. PMID 25858803.
  2. ^ a b c d e Syn NL, Teng MW, Mok TS, Soo RA (December 2017). "De-novo and acquired resistance to immune checkpoint targeting". The Lancet. Oncology. 18 (12): e731–e741. doi:10.1016/s1470-2045(17)30607-1. PMID 29208439.
  3. ^ a b Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD (November 2002). "Cancer immunoediting: from immunosurveillance to tumor escape". Nature Immunology. 3 (11): 991–8. doi:10.1038/ni1102-991. PMID 12407406.
  4. ^ Burnet M (April 1957). "Cancer; a biological approach. I. The processes of control". British Medical Journal. 1 (5022): 779–86. doi:10.1136/bmj.1.3356.779. JSTOR 25382096. PMC 1973174. PMID 13404306.
  5. ^ Kim R, Emi M, Tanabe K (May 2007). "Cancer immunoediting from immune surveillance to immune escape". Immunology. 121 (1): 1–14. doi:10.1111/j.1365-2567.2007.02587.x. PMC 2265921. PMID 17386080.
  6. ^ Pandolfi F, Cianci R, Pagliari D, Casciano F, Bagalà C, Astone A, Landolfi R, Barone C (2011). "The immune response to tumors as a tool toward immunotherapy". Clinical & Developmental Immunology. 2011: 894704. doi:10.1155/2011/894704. PMID 22190975.
  7. ^ a b c Storkus WJ, Finn OJ, DeLeo A, Zarour HM (2003). "Categories of Tumor Antigens". Holland-Frei Cancer Medicine (6th ed.).
  8. ^ Ramos CA, Narala N, Vyas GM, Leen AM, Gerdemann U, Sturgis EM, Anderson ML, Savoldo B, Heslop HE, Brenner MK, Rooney CM (January 2013). "Human papillomavirus type 16 E6/E7-specific cytotoxic T lymphocytes for adoptive immunotherapy of HPV-associated malignancies". Journal of Immunotherapy. 36 (1): 66–76. doi:10.1097/CJI.0b013e318279652e. PMC 3521877. PMID 23211628.
  9. ^ Kelly GL, Stylianou J, Rasaiyaah J, Wei W, Thomas W, Croom-Carter D, Kohler C, Spang R, Woodman C, Kellam P, Rickinson AB, Bell AI (March 2013). "Different patterns of Epstein-Barr virus latency in endemic Burkitt lymphoma (BL) lead to distinct variants within the BL-associated gene expression signature". Journal of Virology. 87 (5): 2882–94. doi:10.1128/JVI.03003-12. PMC 3571367. PMID 23269792.
  10. ^ Disis ML, Cheever MA (October 1996). "Oncogenic proteins as tumor antigens". Current Opinion in Immunology. 8 (5): 637–42. PMID 8902388.
  11. ^ Finn OJ (May 2017). "Human Tumor Antigens Yesterday, Today, and Tomorrow". Cancer Immunology Research. 5 (5): 347–354. doi:10.1158/2326-6066.CIR-17-0112. PMC 5490447. PMID 28465452.
  12. ^ Orell SR, Dowling KD (November 1983). "Oncofetal antigens as tumor markers in the cytologic diagnosis of effusions". Acta Cytologica. 27 (6): 625–9. PMID 6196931.
  13. ^ Hsieh MY, Lu SN, Wang LY, Liu TY, Su WP, Lin ZY, Chuang WL, Chen SC, Chang WY (November 1992). "Alpha-fetoprotein in patients with hepatocellular carcinoma after transcatheter arterial embolization". Journal of Gastroenterology and Hepatology. 7 (6): 614–7. PMID 1283085.
  14. ^ Khoo SK, MacKay EV (October 1976). "Carcinoembryonic antigen (CEA) in ovarian cancer: factors influencing its incidence and changes which occur in response to cytotoxic drugs". British Journal of Obstetrics and Gynaecology. 83 (10): 753–9. PMID 990213.
  15. ^ Wang B, Zaidi N, He LZ, Zhang L, Kuroiwa JM, Keler T, Steinman RM (March 2012). "Targeting of the non-mutated tumor antigen HER2/neu to mature dendritic cells induces an integrated immune response that protects against breast cancer in mice". Breast Cancer Research. 14 (2): R39. doi:10.1186/bcr3135. PMC 3446373. PMID 22397502.
  16. ^ Li G, Wong AJ (September 2008). "EGF receptor variant III as a target antigen for tumor immunotherapy". Expert Review of Vaccines. 7 (7): 977–85. doi:10.1586/14760584.7.7.977. PMID 18767947.
  17. ^ Weon JL, Potts PR (December 2015). "The MAGE protein family and cancer". Current Opinion in Cell Biology. 37: 1–8. doi:10.1016/j.ceb.2015.08.002. PMC 4688208. PMID 26342994.
  18. ^ Dunn GP, Old LJ, Schreiber RD (2004-03-19). "The three Es of cancer immunoediting". Annual Review of Immunology. 22 (1): 329–60. doi:10.1146/annurev.immunol.22.012703.104803. PMID 15032581.
  19. ^ a b Mittal D, Gubin MM, Schreiber RD, Smyth MJ (April 2014). "New insights into cancer immunoediting and its three component phases--elimination, equilibrium and escape". Current Opinion in Immunology. 27: 16–25. doi:10.1016/j.coi.2014.01.004. PMC 4388310. PMID 24531241.
  20. ^ von Boehmer L, Mattle M, Bode P, Landshammer A, Schäfer C, Nuber N, Ritter G, Old L, Moch H, Schäfer N, Jäger E, Knuth A, van den Broek M (2013-07-15). "NY-ESO-1-specific immunological pressure and escape in a patient with metastatic melanoma". Cancer Immunity. 13: 12. PMC 3718732. PMID 23882157.
  21. ^ a b c Daniyan AF, Brentjens RJ (June 2017). "Immunotherapy: Hiding in plain sight: immune escape in the era of targeted T-cell-based immunotherapies". Nature Reviews. Clinical Oncology. 14 (6): 333–334. doi:10.1038/nrclinonc.2017.49. PMC 5536112. PMID 28397826.
  22. ^ Mojic M, Takeda K, Hayakawa Y (December 2017). "The Dark Side of IFN-γ: Its Role in Promoting Cancer Immunoevasion". International Journal of Molecular Sciences. 19 (1): 89. doi:10.3390/ijms19010089. PMC 5796039. PMID 29283429.
  23. ^ Tirapu I, Huarte E, Guiducci C, Arina A, Zaratiegui M, Murillo O, Gonzalez A, Berasain C, Berraondo P, Fortes P, Prieto J, Colombo MP, Chen L, Melero I (February 2006). "Low surface expression of B7-1 (CD80) is an immunoescape mechanism of colon carcinoma". Cancer Research. 66 (4): 2442–50. doi:10.1158/0008-5472.CAN-05-1681. PMID 16489051.
  24. ^ Pettit SJ, Ali S, O'Flaherty E, Griffiths TR, Neal DE, Kirby JA (April 1999). "Bladder cancer immunogenicity: expression of CD80 and CD86 is insufficient to allow primary CD4+ T cell activation in vitro". Clinical and Experimental Immunology. 116 (1): 48–56. doi:10.1046/j.1365-2249.1999.00857.x. PMC 1905215. PMID 10209504.
  25. ^ Peter ME, Hadji A, Murmann AE, Brockway S, Putzbach W, Pattanayak A, Ceppi P (April 2015). "The role of CD95 and CD95 ligand in cancer". Cell Death and Differentiation. 22 (4): 549–59. doi:10.1038/cdd.2015.3. PMC 4356349. PMID 25656654.
  26. ^ Ha TY (December 2009). "The role of regulatory T cells in cancer". Immune Network. 9 (6): 209–35. doi:10.4110/in.2009.9.6.209. PMC 2816955. PMID 20157609.
  27. ^ a b Obeid M, Tesniere A, Ghiringhelli F, Fimia GM, Apetoh L, Perfettini JL, Castedo M, Mignot G, Panaretakis T, Casares N, Métivier D, Larochette N, van Endert P, Ciccosanti F, Piacentini M, Zitvogel L, Kroemer G (Jan 2007). "Calreticulin exposure dictates the immunogenicity of cancer cell death". Nature Medicine. 13 (1): 54–61. doi:10.1038/nm1523. PMID 17187072.
  28. ^ Steinman RM, Mellman I (Jul 2004). "Immunotherapy: bewitched, bothered, and bewildered no more". Science. 305 (5681): 197–200. doi:10.1126/science.1099688. PMID 15247468.
  29. ^ Lake RA, van der Most RG (Jun 2006). "A better way for a cancer cell to die". The New England Journal of Medicine. 354 (23): 2503–4. doi:10.1056/NEJMcibr061443. PMID 16760453.
  30. ^ Zitvogel L, Tesniere A, Kroemer G (Oct 2006). "Cancer despite immunosurveillance: immunoselection and immunosubversion". Nature Reviews. Immunology. 6 (10): 715–27. doi:10.1038/nri1936. PMID 16977338.
  31. ^ Zitvogel L, Casares N, Péquignot MO, Chaput N, Albert ML, Kroemer G (2004). Immune response against dying tumor cells. Advances in Immunology. 84. pp. 131–79. doi:10.1016/S0065-2776(04)84004-5. ISBN 978-0-12-022484-5. PMID 15246252.
  32. ^ Bellamy CO, Malcomson RD, Harrison DJ, Wyllie AH (Feb 1995). "Cell death in health and disease: the biology and regulation of apoptosis". Seminars in Cancer Biology. 6 (1): 3–16. doi:10.1006/scbi.1995.0002. PMID 7548839.
  33. ^ Thompson CB (Mar 1995). "Apoptosis in the pathogenesis and treatment of disease". Science. 267 (5203): 1456–62. doi:10.1126/science.7878464. PMID 7878464.
  34. ^ Igney FH, Krammer PH (Apr 2002). "Death and anti-death: tumour resistance to apoptosis". Nature Reviews. Cancer. 2 (4): 277–88. doi:10.1038/nrc776. PMID 12001989.
  35. ^ Steinman RM, Turley S, Mellman I, Inaba K (Feb 2000). "The induction of tolerance by dendritic cells that have captured apoptotic cells". The Journal of Experimental Medicine. 191 (3): 411–6. doi:10.1084/jem.191.3.411. PMC 2195815. PMID 10662786.
  36. ^ Liu K, Iyoda T, Saternus M, Kimura Y, Inaba K, Steinman RM (Oct 2002). "Immune tolerance after delivery of dying cells to dendritic cells in situ". The Journal of Experimental Medicine. 196 (8): 1091–7. doi:10.1084/jem.20021215. PMC 2194037. PMID 12391020.
  37. ^ Kroemer G, El-Deiry WS, Golstein P, Peter ME, Vaux D, Vandenabeele P, Zhivotovsky B, Blagosklonny MV, Malorni W, Knight RA, Piacentini M, Nagata S, Melino G (Nov 2005). "Classification of cell death: recommendations of the Nomenclature Committee on Cell Death". Cell Death and Differentiation. 12 Suppl 2: 1463–7. doi:10.1038/sj.cdd.4401724. PMID 16247491.
  38. ^ Buckwalter MR, Srivastava PK (2013). "Mechanism of dichotomy between CD8+ responses elicited by apoptotic and necrotic cells". Cancer Immunity. 13: 2. PMC 3559190. PMID 23390373.
  39. ^ Gamrekelashvili J, Ormandy LA, Heimesaat MM, Kirschning CJ, Manns MP, Korangy F, Greten TF (Oct 2012). "Primary sterile necrotic cells fail to cross-prime CD8(+) T cells". Oncoimmunology. 1 (7): 1017–1026. doi:10.4161/onci.21098. PMC 3494616. PMID 23170250.
  40. ^ Janssen E, Tabeta K, Barnes MJ, Rutschmann S, McBride S, Bahjat KS, Schoenberger SP, Theofilopoulos AN, Beutler B, Hoebe K (Jun 2006). "Efficient T cell activation via a Toll-Interleukin 1 Receptor-independent pathway". Immunity. 24 (6): 787–99. doi:10.1016/j.immuni.2006.03.024. PMID 16782034.
  41. ^ Ronchetti A, Rovere P, Iezzi G, Galati G, Heltai S, Protti MP, Garancini MP, Manfredi AA, Rugarli C, Bellone M (Jul 1999). "Immunogenicity of apoptotic cells in vivo: role of antigen load, antigen-presenting cells, and cytokines". Journal of Immunology. 163 (1): 130–6. PMID 10384108.
  42. ^ Scheffer SR, Nave H, Korangy F, Schlote K, Pabst R, Jaffee EM, Manns MP, Greten TF (Jan 2003). "Apoptotic, but not necrotic, tumor cell vaccines induce a potent immune response in vivo". International Journal of Cancer. 103 (2): 205–11. doi:10.1002/ijc.10777. PMID 12455034.
  43. ^ Storkus WJ, Falo LD (Jan 2007). "A 'good death' for tumor immunology". Nature Medicine. 13 (1): 28–30. doi:10.1038/nm0107-28. PMID 17206130.
  44. ^ Dunn GP, Koebel CM, Schreiber RD (Nov 2006). "Interferons, immunity and cancer immunoediting". Nature Reviews. Immunology. 6 (11): 836–48. doi:10.1038/nri1961. PMID 17063185.