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The role of the Major Histocompatibility Complex in the spread of contagious cancers

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Abstract

Major Histocompatibility Complex (MHC) genes play a key role in immune response to infectious diseases, immunosurveillance, and self/nonself recognition. Matching MHC alleles is critical for organ transplantation, while changes in the MHC profile of tumour cells allow effective evasion of the immune response. Two unique cancers have exploited these features to become transmissible. In this review I discuss the functional role of MHC molecules in the emergence and evolution of Devil Facial Tumour Disease (DFTD) and Canine Transmissible Venereal Tumour (CTVT). High levels of genetic diversity at MHC genes play a critical role in protecting populations of vertebrate species from contagious cancer. However, species that have undergone genetic bottlenecks and have lost diversity at MHC genes are at risk of transmissible tumours. Moreover, evolution and selection for tumour variants capable of evading the immune response allow contagious cancers to cross MHC barriers. Transmissible cancers are rare but they can provide unique insights into the genetics and immunology of tumours and organ transplants.

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References

  • Adams EW, Sapp WJ, Carter LP (1981) Cytogenetic observations on the canine venereal tumor in long term culture. Cornell Vet 71:336–346

    CAS  PubMed  Google Scholar 

  • Algarra I, Cabrera T, Garrido F (2000) The HLA crossroad in tumor immunology. Hum Immunol 61:65–73

    Article  CAS  PubMed  Google Scholar 

  • Algarra I, Garcia-Lora A, Cabrera T, Ruiz-Cabello F, Garrido F (2004) The selection of tumor variants with altered expression of classical and nonclassical MHC Class I molecules: implications for tumor immune escape. Cancer Immunol Immunother 53:904–910

    Article  CAS  PubMed  Google Scholar 

  • Banfield WG, Woke PA, MacKay CM, Cooper HL (1965) Mosquito transmission of a reticulum cell sarcoma of hamsters. Science 148:1239–1240

    Article  CAS  PubMed  Google Scholar 

  • Bradley BA (1991) The role of HLA matching in transplantation. Immunol Lett 29:55–59

    Article  CAS  PubMed  Google Scholar 

  • Brindley DC, Banfield WG (1961) A contagious tumor of the hamster. J Natl Cancer Inst 26:949–957

    Google Scholar 

  • Bubenik J (2004) MHC Class I down-regulation: tumour escape from immune surveillance? Int J Oncol 25:487-491 (review)

    Google Scholar 

  • Burnet FM (1957) Cancer—a biological approach. Br Med J 1:841–847

    Article  CAS  PubMed  Google Scholar 

  • Buss LW (1982) Somatic cell parasitism and the evolution of somatic tissue compatibility. Proc Natl Acad Sci USA 79:5337–5341

    Article  CAS  PubMed  Google Scholar 

  • Cabrera T, Lopez-Nevot MA, Gaforio JJ, Ruiz-Cabello F, Garrido F (2003) Analysis of HLA expression in human tumor tissues. Cancer Immunol Immunother 52:1–9

    CAS  PubMed  Google Scholar 

  • Cohen D, Shalev A, Krup M (1984) Lack of beta 2 microglobulin on the surface of canine transmissible venereal tumor cells. J Natl Cancer Inst 72:395–401

    CAS  PubMed  Google Scholar 

  • Das U, Das AK (2000) Review of canine transmissible venereal sarcoma. Vet Res Commun 24:545–556

    Article  CAS  PubMed  Google Scholar 

  • Dausset J, Rapaport FT, Colombani J, Feingold N (1965) A leucocyte group and its relationship to tissue histocompatibility in man. Transplantation 3:701–705

    Article  CAS  PubMed  Google Scholar 

  • De Monbreun WA, Goodpasturem EW (1934) An experimental investigation concerning the nature of contagious lymphosarcoma in dogs. Am J Cancer 21:295–321

    Google Scholar 

  • De Tomaso AW, Nyholm SV, Palmeri KJ, Ishizuka KJ, Ludington WB et al (2005) Isolation and characterization of a protochordate histocompatibility locus. Nature 438:454–459

    Article  PubMed  Google Scholar 

  • Dingli D, Nowak MA (2006) Cancer biology: infectious tumour cells. Nature 443:35–36

    Article  CAS  PubMed  Google Scholar 

  • Fassati A, Mitchison NA (2010) Testing the theory of immune selection in cancers that break the rules of transplantation. Cancer Immunol Immunother 59:643–651

    Article  CAS  PubMed  Google Scholar 

  • Ferrone S, Marincola FM (1995) Loss of HLA class I antigens by melanoma cells: molecular mechanisms, functional significance and clinical relevance. Immunol Today 16:487–494

    Article  CAS  PubMed  Google Scholar 

  • Garcia-Lora A, Algarra I, Garrido F (2003) MHC class I antigens, immune surveillance, and tumor immune escape. J Cell Physiol 195:346–355

    Article  CAS  PubMed  Google Scholar 

  • Guiler ER (1992) The Tasmanian devil. St David’s Park Publishing, Hobart

    Google Scholar 

  • Hsiao YW, Liao KW, Hung SW, Chu RM (2002) Effect of tumor infiltrating lymphocytes on the expression of MHC molecules in canine transmissible venereal tumor cells. Vet Immunol Immunopathol 87:19–27

    Article  CAS  PubMed  Google Scholar 

  • Hsiao YW, Liao KW, Hung SW, Chu RM (2004) Tumor-infiltrating lymphocyte secretion of IL-6 antagonizes tumor-derived TGF-beta 1 and restores the lymphokine-activated killing activity. J Immunol 172:1508–1514

    CAS  PubMed  Google Scholar 

  • Hsiao YW, Liao KW, Chung TF, Liu CH, Hsu CD et al (2008) Interactions of host IL-6 and IFN-gamma and cancer-derived TGF-beta1 on MHC molecule expression during tumor spontaneous regression. Cancer Immunol Immunother 57:1091–1104

    Article  CAS  PubMed  Google Scholar 

  • Isoda T, Ford AM, Tomizawa D, van Delft FW, De Castro DG et al (2009) Immunologically silent cancer clone transmission from mother to offspring. Proc Natl Acad Sci USA 106:17882–17885

    Article  PubMed  Google Scholar 

  • Johnson C (2006) Australia’s mammal extinctions: a 50000 year history. Cambridge University Press, Melbourne

    Google Scholar 

  • Jones ME, Paetkau D, Gefen E, Moritz C (2004) Genetic diversity and population structure of Tasmanian devils, the largest marsupial carnivore. Mol Ecol 13:2197–2209

    Article  CAS  PubMed  Google Scholar 

  • Kauffman HM, McBride MA, Cherikh WS, Spain PC, Delmonico FL (2002) Transplant tumor registry: donors with central nervous system tumors1. Transplantation 73:579–582

    Article  PubMed  Google Scholar 

  • Kelley J, Walter L, Trowsdale J (2005) Comparative genomics of major histocompatibility complexes. Immunogenetics 56:683–695

    Article  CAS  PubMed  Google Scholar 

  • Kennedy LJ, Angles JM, Barnes A, Carmichael LE, Radford AD et al (2007a) DLA-DRB1, DQA1, and DQB1 alleles and haplotypes in North American Gray Wolves. J Hered 98:491–499

    Article  CAS  PubMed  Google Scholar 

  • Kennedy LJ, Barnes A, Short A, Brown JJ, Lester S et al. (2007b) Canine DLA diversity: 1. New alleles and haplotypes. Tissue Antigens 69 Suppl 1:272-288

  • Kurbel S, Plestina S, Vrbanec D (2007) Occurrence of the acquired immunity in early vertebrates due to danger of transmissible cancers similar to canine venereal tumors. Med Hypotheses 68:1185–1186

    Article  PubMed  Google Scholar 

  • Lakkis FG, Dellaporta SL, Buss LW (2008) Allorecognition and chimerism in an invertebrate model organism. Organogenesis 4:236–240

    Article  PubMed  Google Scholar 

  • LaRosa DF, Rahman AH, Turka LA (2007) The innate immune system in allograft rejection and tolerance. J Immunol 178:7503–7509

    CAS  PubMed  Google Scholar 

  • Lefebvre S, Antoine M, Uzan S, McMaster M, Dausset J et al (2002) Specific activation of the non-classical class I histocompatibility HLA-G antigen and expression of the ILT2 inhibitory receptor in human breast cancer. J Pathol 196:266–274

    Article  CAS  PubMed  Google Scholar 

  • Liao KW, Lin ZY, Pao HN, Kam SY, Wang FI et al (2003) Identification of canine transmissible venereal tumor cells using in situ polymerase chain reaction and the stable sequence of the long interspersed nuclear element. J Vet Diagn Invest 15:399–406

    PubMed  Google Scholar 

  • Ljunggren HG, Karre K (1990) In search of the ‘missing self’: MHC molecules and NK cell recognition. Immunol Today 11:237–244

    Article  CAS  PubMed  Google Scholar 

  • Loh R, Bergfeld J, Hayes D, O’Hara A, Pyecroft S et al (2006a) The pathology of devil facial tumor disease (DFTD) in Tasmanian Devils (Sarcophilus harrisii). Vet Pathol 43:890–895

    Article  CAS  PubMed  Google Scholar 

  • Loh R, Hayes D, Mahjoor A, O’Hara A, Pyecroft S et al (2006b) The immunohistochemical characterization of devil facial tumor disease (DFTD) in the Tasmanian Devil (Sarcophilus harrisii). Vet Pathol 43:896–903

    Article  CAS  PubMed  Google Scholar 

  • McCallum H (2008) Tasmanian devil facial tumour disease: lessons for conservation biology. Trends Ecol Evol 23:631–637

    Article  PubMed  Google Scholar 

  • McCallum H, Tompkins DM, Jones ME, Lachish S, Marvenek S et al (2007) Distribution and impacts of Tasmanian devil facial tumour disease. EcoHealth 4:318–325

    Article  Google Scholar 

  • McKitrick TR, De Tomaso AW (2010) Molecular mechanisms of allorecognition in a basal chordate. Semin Immunol 22:34–38

    Article  CAS  PubMed  Google Scholar 

  • Moffett A, Loke C (2006) Immunology of placentation in eutherian mammals. Nat Rev Immunol 6:584–594

    Article  CAS  PubMed  Google Scholar 

  • Murchison EP (2009) Clonally transmissible cancers in dogs and Tasmanian devils. Oncogene 27:S19–S30

    Article  Google Scholar 

  • Murchison EP, Tovar C, Hsu A, Bender HS, Kheradpour P et al (2010) The Tasmanian devil transcriptome reveals Schwann cell origins of a clonally transmissible cancer. Science 327:84–87

    Article  CAS  PubMed  Google Scholar 

  • Murgia C, Pritchard JK, Kim SY, Fassati A, Weiss RA (2006) Clonal origin and evolution of a transmissible cancer. Cell 126:477–487

    Article  CAS  PubMed  Google Scholar 

  • Nicotra ML, Powell AE, Rosengarten RD, Moreno M, Grimwood J et al (2009) A hypervariable invertebrate allodeterminant. Curr Biol 19:583–589

    Article  CAS  PubMed  Google Scholar 

  • Novinski MA (1876) Zur Frage uber die Impfung der Krebsigen Gescgwulste. Zentralbl Med Wissensch 14:790–791

    Google Scholar 

  • O’Brien SJ, Roelke ME, Marker L, Newman A, Winkler CA et al (1985) Genetic basis for species vulnerability in the cheetah. Science 227:1428–1434

    Article  PubMed  Google Scholar 

  • O’Neill ID (2010) Tasmanian devil facial tumor disease: insights into reduced tumor surveillance from an unusual malignancy. Int J Cancer 127(7):1637–1642

    PubMed  Google Scholar 

  • Obendorf D, McGlashan ND (2008) Research priorities in the Tasmanian devil facial tumour debate. Eur J Oncol 13:229–238

    Google Scholar 

  • Pangault C, Amiot L, Caulet-Maugendre S, Brasseur F, Burtin F et al (1999) HLA-G protein expression is not induced during malignant transformation. Tissue Antigens 53:335–346

    Article  CAS  PubMed  Google Scholar 

  • Pearse AM, Swift K (2006) Allograft theory: transmission of devil facial-tumour disease. Nature 439:549

    Article  CAS  PubMed  Google Scholar 

  • Pyecroft S, Pearse AM, Loh R, Swift K, Belov K et al (2007) Towards a case definition for Devil Facial Tumour Disease: what is it? EcoHealth 4:346–351

    Article  Google Scholar 

  • Radwan J, Biedrzycka A, Babik W (2010) Does reduced MHC diversity decrease viability of vertebrate populations? Biol Conserv 143:537–544

    Article  Google Scholar 

  • Rebbeck CA, Thomas R, Breen M, Leroi AM, Burt A (2009) Origins and evolution of a transmissible cancer. Evolution 63:2340–2349

    Article  CAS  PubMed  Google Scholar 

  • Rosa SF, Powell AE, Rosengarten RD, Nicotra ML, Moreno MA et al (2010) Hydractinia allodeterminant alr1 resides in an immunoglobulin superfamily-like gene complex. Curr Biol 20:1122–1127

    Article  CAS  PubMed  Google Scholar 

  • Rust JH (1949) Transmissible lymphosarcoma in the dog. J Am Vet Med Assoc 114:10–14

    CAS  PubMed  Google Scholar 

  • Scanlon EF, Hawkins RA, Fox WW, Smith WS (1965) Fatal homotransplanted melanoma. Cancer 18:782–789

    Article  CAS  PubMed  Google Scholar 

  • Siddle HV, Kreiss A, Eldridge MD, Noonan E, Clarke CJ et al (2007) Transmission of a fatal clonal tumor by biting occurs due to depleted MHC diversity in a threatened carnivorous marsupial. Proc Natl Acad Sci USA 104(41):16221–16226

    Article  CAS  PubMed  Google Scholar 

  • Siddle H, Deakin J, Coggill P, Hart E, Cheng Y et al (2009) MHC-linked and un-linked class I genes in the wallaby. BMC Genomics 10:310

    Article  PubMed  Google Scholar 

  • Siddle HV, Marzec J, Cheng Y, Jones M, Belov K (2010) MHC gene copy number variations in Tasmanian devils: implications for the spread of a contagious cancer. Proc Biol Sci 277(1690):2001–2006

    Article  CAS  PubMed  Google Scholar 

  • Snell GD (1953) The genetics of transplantation. J Natl Cancer Inst 14:691-700; discussion 701-694

    Google Scholar 

  • Stoner DS, Weissman IL (1996) Somatic and germ cell parasitism in a colonial ascidian: possible role for a highly polymorphic allorecognition system. Proc Natl Acad Sci USA 93:15254–15259

    Article  CAS  PubMed  Google Scholar 

  • Thomas L (1959) Cellular and humoral aspects of the hypersensitive states. Hoeber-Harper, New York

    Google Scholar 

  • Ugurel S, Reinhold U, Tilgen W (2002) HLA-G in melanoma: a new strategy to escape from immunosurveillance? Onkologie 25:129–134

    Article  CAS  PubMed  Google Scholar 

  • Vincent MD (2010) The animal within: carcinogenesis and the clonal evolution of cancer cells are speciation events sensu stricto. Evolution 64:1173–1183

    Article  PubMed  Google Scholar 

  • Warrens AN, Lombardi G, Lechler RI (1994) Presentation and recognition of major and minor histocompatibility antigens. Transpl Immunol 2:103–107

    Article  CAS  PubMed  Google Scholar 

  • Wood GM, Kreiss A, Belov K, Siddle HV, Obendorf DL et al (2007) The immune response of the Tasmanian devil (Sarcophilus harrisii) and Devil Facial Tumour Disease. EcoHealth 4(3):338–345

    Article  Google Scholar 

  • Wright DH, Peel S, Cooper EH, Huges DT (1970) Transmissible venereal sarcoma of dogs. A histochemical and chromosomal analysis of tumours in Uganda. Eur J Clin Biol Res 15:155

    Google Scholar 

  • Yang TJ, Chandler JP, Dunne-Anway S (1987) Growth stage dependent expression of MHC antigens on the canine transmissible venereal sarcoma. Br J Cancer 55:131–134

    Article  CAS  PubMed  Google Scholar 

  • Zitvogel L, Tesniere A, Kroemer G (2006) Cancer despite immunosurveillance: immunoselection and immunosubversion. Nat Rev Immunol 6:715–727

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

My research and the ideas developed in this review have been greatly influenced by my amazing students and my fabulous collaborators, including Hannah Siddle, Menna Jones, Greg Woods, Alex Kreiss, Anne-Maree Pearse, and Hamish McCallum. I thank two anonymous reviewers for comments that improved this manuscript. My research is funded by the Australian Research Council, the University of Sydney, and the Save the Tasmanian Devil Appeal.

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  1. Faculty of Veterinary Science, RMC Gunn B19, University of Sydney, Sydney, NSW, 2006, Australia

    Katherine Belov

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Correspondence to Katherine Belov.

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Belov, K. The role of the Major Histocompatibility Complex in the spread of contagious cancers. Mamm Genome 22, 83–90 (2011). https://doi.org/10.1007/s00335-010-9294-2

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