HLA Class-II Expression in Human Tumors

  • Federico Garrido
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1151)


HLA class II molecules play a pivotal role in antigen presentation to T lymphocytes. This chapter analyzed the expression of these molecules in different human tumors and their role in cancer progression. The possible connection between tumor HLA class II expression and the pathogenesis of autoimmune diseases is discussed.


HLA-II in tissues HLA-II in tumors Antigen presenting cells Interferon Tumor rejection Tumor prognosis HLA-II & autoimmunity Immunohistochemistry Tumor infiltrating lymphocytes Cytokynes 


  1. Andersen SN, Rognum TO, Lund E, Meling GI, Hauge S (1993) Strong HLA-DR expression in large bowel carcinomas is associated with good prognosis. Br J Cancer 68:80–85CrossRefGoogle Scholar
  2. Botazzo F, Dean BM, McNally JM, MacKay EH, Swift PG, Gamble DR (1985) In situ characterization of autoimmune phenomena and expression of HLA molecules in the pancreas in diabetes insulitis. N Engl J Med 313(6):353–360CrossRefGoogle Scholar
  3. Brocker EB, Suter L, Bruggen J, Ruiter DJ, Macher E, Sorg C (1985) Phenotypic dinamics of tumour progression in human malignant melanoma. Int J Cancer 36:29–35CrossRefGoogle Scholar
  4. Brunner CA, Gokel JM, Riethmuller G, Johnson JP (1991) Expression of HLA-D subloci DR and DQ by breast carcinomas is correlated with distinct parameters of favourable prognosis. Eur J Cancer 27:411–416CrossRefGoogle Scholar
  5. Cabrera T, Garrido V, Concha A, Martin J, Esquivias J, Oliva MR, Ruiz-Cabello F, Serrano S, Garrido F (1992) HLA molecules in basal cell carcinoma of the skin. Immunobiology 185:440–452CrossRefGoogle Scholar
  6. Cabrera T, Ruiz-Cabello F, Garrido F (1995) Biological implications of HLA-DR expression in tumours. Scand J Immunol 41:398–406CrossRefGoogle Scholar
  7. Chen P, Ullrich S, Ananthaswamy H (1994) Presentation of endogenous tumor antigens to CD4+ T lymphocytes by murine melanoma cells transfected with major histocompatibility complex class II genes. J Leukocyte Biol 56:469–474CrossRefGoogle Scholar
  8. Concha A, Esteban F, Cabrera T, Ruiz-Cabello F, Garrido F (1991) Tumor aggressiveness and MHC class I and II antigens in laryngeal and breast cancer. Semin Cancer Biol 2:47–54PubMedGoogle Scholar
  9. Concha A, Ruiz-Cabello F, Cabrera T, Nogales F, Collado A, Garrido F (1995) Different patterns of HLA-DR antigen expression in normal epithelium, hyperplastic and neoplastic malignant lesions of the breast. Eur J Immunogenet 22:299–310CrossRefGoogle Scholar
  10. D’Alessandro G, Zardawi I, Grace J, McCarthy WH, Hersey P (1987) Immunohistological evaluation of MHC class I and II antigen expression on nevi and melanoma: relation to biology of melanoma. Pathology 19:339–346CrossRefGoogle Scholar
  11. Daar AS, Fuggle SV, Ting A, Fabre JW (1982) Anomalous expression of HLA DR antigens on human colorectal cancer cells. J Immunol 129:447PubMedGoogle Scholar
  12. Daar AS, Fuggle SV, Fabre JW, Ting A, Morris P (1984) The detail distribution of MHC class II antigens in normal human organs. Transplantation 38:293–298CrossRefGoogle Scholar
  13. Degener T, Momburg F, Moller P (1998) Differential expression of HLA-DR, HLA-DP, HLA-DQ and associated invariant chain (II) in normal colorectal mucosa, adenoma and carcinoma. Virchows Arch A 412:315–322CrossRefGoogle Scholar
  14. Esteban F, Ruiz-Cabello F, Concha A, Perez-Ayala M, Sanchez-Rozas JA, Garrido F (1990) HLA-DR expression is associated with excellent prognosis in squamous cell carcinoma of the larynx. Clin Exp Metastasis 8:319–328CrossRefGoogle Scholar
  15. Ferron A, Perez-Ayala M, Concha A, Cabrera T, Redondo M, Oliva MR, Ruiz-Cabello F, Garrido F (1989) MHC class I and II antigens on gastric carcinomas and autologous mucosa. J Immunogenet 16:413–423CrossRefGoogle Scholar
  16. Garrido F, Cabrera T, Concha A, Glew S, Ruiz-Cabello F, Stern PL (1993) Natural history of HLA expression during tumour development. Immunol Today 14:491–499CrossRefGoogle Scholar
  17. Ghosh AK, Moore M, Street AJ, Howat JMT, Schofield PF (1986) Expression of HLA-D subregion products on human colorectal carcinoma. Int J Cancer 38:459–464CrossRefGoogle Scholar
  18. Glew SS, Duggan-Keen M, Cabrera T, Stern P (1992) HLA class II antigen expression in human papillomavirus associated cervical cancer. Cancer Res 52:1–8Google Scholar
  19. Gutierrez J, Lopez-Nevot MA, Cabrera T, Oliva R, Esquivias J, Ruiz-Cabello F, Garrido F (1987) Class I ans II HLA antigen distribution in normal mucosa, adenoma and colon carcinoma: relation with malignancy and invasiveness. Exp Clin Immunogenet 4:144–152PubMedGoogle Scholar
  20. Gutierrez J, Ruiz-Cabello F, Lopez-Nevot MA, Cabrera T, Esquivias J, Garrido F (1990) Class II HLA antigen expression in familial polyposis coli is related to the degree of dysplasia. Immunobiology 180:138–148CrossRefGoogle Scholar
  21. Hasegawa SL, James LR, Sloan JH, Boos JM (1993) Protease treatment of nuclear extracts distinguishes between class II major histocompatibility complex X1 box DNA-binding proteins in wild type and class II deficient B cells. J Immunol 150:1781–1793PubMedGoogle Scholar
  22. Jansson R, Karlsson A, Forsum U (1984) Intrathyroidal HLA-DR expression and T lymphocyte phenotypes in Graves’s thyrotoxicosis, Hasimoto’s thyroiditis and nodular colloid goitre. Clin Exp Immunol 58:264–272PubMedPubMedCentralGoogle Scholar
  23. Lopez-Nevot MA, Garcia E, Pareja E, Bonal E, Martin F, Ruiz-Cabello F, Serrano S, Garrido F (1986) Differential expression of HLA class I and II antigens in primary and metastatic melanomas. J Immunogenet 13(2/3):219–228CrossRefGoogle Scholar
  24. Lopez-Nevot MA, Garcia E, Romero C, Oliva MR, Serrano S, Garrido F (1988) Phenotypic and genetic analysis of HLA class I and HLA-DR antigen expression on human melanomas. Exp Clin Immunogenet 5:203–212PubMedGoogle Scholar
  25. Lundin K, Sollid L (2014) Advances in celiac disease. Curr Opin Gastroenterol 30(2):154–162CrossRefGoogle Scholar
  26. Michel S, Linnebacher M, Alcañiz J, Voss M, Wagner R, Dippold W, Becker C, von Knebel Doeberitz M, Ferrone M, Kloor M (2010) Lack of HLA class II antigen expression in microsatellite unstable colorectal carcinomas is caused by mutations in HLA class II regulatory genes. Int J Cancer 127(4):889–898PubMedPubMedCentralGoogle Scholar
  27. Momburg F, Herrmann B, Moldehauer G, Moller PB (1987) B cell lymphomas of high-grade malignancy frequently lack HLA-DR, DP and DQ antigens and associated invariant chain. Int J Cancer 40:598–603CrossRefGoogle Scholar
  28. Moore M, Ghosh D, Johnston D, Street J (1986) Expression of MHC class II products on human colorectal cancer: an immunohistological and flow cytometric study. J Immunogenet 13:201–209CrossRefGoogle Scholar
  29. Natali PG, De Martino C, Quaranta V, Nicotra MR, Frezza F, Pellegrino MA, Ferrone S (1981) Expression of Ia like antigens in normal human non-lymphoid tissues. Transplantation 31:75–78CrossRefGoogle Scholar
  30. Natali PG, Giacomini P, Bigotti A, Imai K, Nicotra MR, Ferrone S (1983) Heterogeneity in the expression of HLA and tumor associated antigens by surgically removed and cultured breast carcinoma cells. Cancer Res 43:660–668PubMedGoogle Scholar
  31. Ostrand-Rosenberg S (2005) CD4+ T lymphocytes: a critical component of antitumor immunity. Cancer Invest 23:413–419PubMedGoogle Scholar
  32. Ostrand-Rosenberg S, Thakur A, Clements V (1990) Rejection of mouse sarcoma cells after transfection of MHC-class II genes. J Immunol 144:4068–4071PubMedGoogle Scholar
  33. Pawelec G, Marsh SG (2006) ESTDAB: a collection of immunologically characterized melanoma cell lines and searchable databank. Cancer Immunol Immunother 55:623–627CrossRefGoogle Scholar
  34. Perea F, Sánchez-Palencia A, Gómez-Morales M, Bernal M, Concha Á, García MM, González-Ramírez AR, Kerick M, Martin J, Garrido F, Ruiz-Cabello F, Aptsiauri N (2018) HLA class I loss and PD-L1 expression in lung cancer: impact on T-cell infiltration and immune escape. Oncotarget 9(3):4120–4133. eCollection 2018 Jan 9. PubMed PMID: 29423109; PubMed Central PMCID: PMC5790526
  35. Redondo M, Concha A, Oldiviela R, Cueto A, Gonzalez A, Garrido F, Ruiz-Cabello (1991) Expression of HLA class I and II antigens in bronchogenic carcinomas: its relationship to cellular DNA content and clinic-pathological parameters. Cancer Res 51:4948–4954PubMedGoogle Scholar
  36. Rodriguez T, Mendez R, De Campo A, Aptsiauri N, Martin J, Orozco G, Pawelec G, Shadendorf D, Ruiz-Cabello F, Garrido F (2007) Patterns of constitutive and IFN-γ inducible expression of HLA class II molecules in human melanoma cell lines. Immunogenetics 59:123–133CrossRefGoogle Scholar
  37. Ruiter DJ, Bhan AK, Harrist TJ, Sober AJ, Mihm MC (1982) Major histocompatibility antigens and mononuclear inflammatory infiltrate in benign nevomelanocytic proliferations and malignant melanoma. J Immunol 129:2808–2815PubMedGoogle Scholar
  38. Ruiter DJ, Bergman W, Welvaart K, Scheffer E, van Vloten WA, Russo C, Ferrone S (1984) Immunohistochemical analysis of malignant melanomas and nevocellular nevi with monoclonal antibodies to distinct monomorphic determinants of HLA antigens. Cancer Res 44:3930–3935PubMedGoogle Scholar
  39. Sarna VK, Lundin KEA, Morkrid L, Qiao SW, Sollid LM, Christophersen A (2018) HLA-DQ-Gluten Tetramer blood test accurately identifies patients with and without celiac disease in absence of gluten consumption. Gastroenterology 154(4):886–896CrossRefGoogle Scholar
  40. Spier CM, Grogan TM, Lippman SM, Slymen DJ, Rybski JA, Miller TP (1988) The aberrancy of immunophenotype and immunoglobuline status as indicators of prognosis in B-cell difuse large-cell lymphoma. Am J Pathol 133:118–126PubMedPubMedCentralGoogle Scholar
  41. Stamnaes I, Sollid LM (2015) Celiac disease: autoimmunity in response to food antigen. Semin Immunol 27(5):343–352CrossRefGoogle Scholar
  42. Stimac E, Urieli-Shoval S, Kempin S, Pious D (1991) Defective HLA- DRA X box binding in the class II trans activator transcription factor mutant 6.1.6 and in cell lines from class II immunedeficient patients. J Immunol 146:4398–4405PubMedGoogle Scholar
  43. Taramelli D, Fosati G, Mazzochi A, Delia D, Ferrone S, Parmiani G (1986) Class I and II HLA and melanoma associated antigen expression and modulation on melanoma cells isolated from primary and metastatic lesions. Cancer Res 46:433–439PubMedGoogle Scholar
  44. Van Duinen SG, Mauw BJ, de Graaff-Reitsma CB, Ruiter DJ (1984) Methods in laboratory investigation: Immunoelectron microscopic methods for demonstration of antigens on normal human melanocytes and other epidermal cells. Lab Invest 50:733–741PubMedGoogle Scholar
  45. Wang E, Worschech A, Marincola FM (2008) The immunological constant of rejection. Trends Immunol 29:256–262CrossRefGoogle Scholar
  46. Wilson BS, Indiveri F, Pellegrino MA, Ferrone S (1979) DR (Ia-like) antigens on human melanoma cells. Serological detection and immunohistochemical characterization. J Exp Med 149:658–668CrossRefGoogle Scholar
  47. Zaloudik J, Moore M, Ghosh AK, Mechl Z, Rejthar A (1988) DNA content and MHC class II antigen expression in malignant melanoma: clinical course. J Clin Pathol 41:1078–1084CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Federico Garrido
    • 1
  1. 1.Departamento de Analisis Clinicos e Inmunologia, Hospital Universitario Virgen de las Nieves, Facultad de MedicinaUniversidad de GranadaGranadaSpain

Personalised recommendations