Biological Implications of HLA‐DR Expression in Tumours

HLA‐DR antigens show restricted tissue distribution in comparison with the more extensive expression of HLA class I molecules. This constitutive expression is genetically controlled by well‐defined mechanisms. In addition, DR antigen expression can be induced by a variety of cytokines through different molecular genetic events that convert DR‐negative epithelia into positive cells. In this review we analyse the two major pathological situations in which abnormal DR expression occurs: autoimmune diseases and tumour development. We hypothesize that conversion to DR‐positivity may produce two opposite effects in both clinical situations: (1) a useful one in tumours associated with a good prognosis; and (2) a harmful one in autoimmune diseases with increased tissue damage.

[1]  W. Knapp,et al.  Immunological features of nonimmunogenic hyperthyroidism. , 1985, The Journal of clinical endocrinology and metabolism.

[2]  M. Mcnulty,et al.  VIRUS-LIKE PARTICLES IN CALVES' FÆCES , 1975, The Lancet.

[3]  S. Ostrand-Rosenberg,et al.  Rejection of mouse sarcoma cells after transfection of MHC class II genes. , 1990, Journal of immunology.

[4]  M. R. Oliva,et al.  MHC CLASS I AND II ANTIGENS ON GASTRIC CARCINOMAS AND AUTOLOGOUS MUCOSA , 1989, Journal of immunogenetics.

[5]  R. Dedrick,et al.  Sequence elements required for activity of a murine major histocompatibility complex class II promoter bind common and cell-type-specific nuclear factors , 1990, Molecular and cellular biology.

[6]  What Triggers Autoimmunity? , 1985, The Lancet.

[7]  C. Cowing,et al.  Does T-cell restriction to Ia limit the need for self-tolerance? , 1985, Immunology today.

[8]  J. Allison,et al.  CD28-mediated signalling co-stimulates murine T cells and prevents induction of anergy in T-cell clones , 1992, Nature.

[9]  A. Ghosh,et al.  Expression of HLA‐D sub‐region products on human colorectal carcinoma , 1986, International journal of cancer.

[10]  P. A. Peterson,et al.  Hormonal regulation of the expression of la antigens on mammary gland epithelium , 1980, European journal of immunology.

[11]  J. Bach,et al.  Molecular and genetic characteristics of pathogenic autoantibodies. , 1989 .

[12]  U. Forsum,et al.  Intrathyroidal HLA-DR expression and T lymphocyte phenotypes in Graves' thyrotoxicosis, Hashimoto's thyroiditis and nodular colloid goitre. , 1984, Clinical and experimental immunology.

[13]  T. Grogan,et al.  The aberrancy of immunophenotype and immunoglobulin status as indicators of prognosis in B cell diffuse large cell lymphoma. , 1988, The American journal of pathology.

[14]  C. Benoist,et al.  A multiplicity of CCAAT box-binding proteins , 1987, Cell.

[15]  F. Garrido,et al.  Class I and II HLA antigen distribution in normal mucosa, adenoma and colon carcinoma: relation with malignancy and invasiveness. , 1987, Experimental and clinical immunogenetics.

[16]  M. Scupoli,et al.  CELL lineage‐specific and developmental stage‐specific controls of MHC class‐II‐antigen expression , 1991, International journal of cancer. Supplement = Journal international du cancer. Supplement.

[17]  I. Todd,et al.  Occurrence of thyrocyte HLA class II expression in a wide variety of thyroid diseases: relationship with lymphocytic infiltration and thyroid autoantibodies. , 1988, The Journal of clinical endocrinology and metabolism.

[18]  D. K. Didier,et al.  Characterization of the cDNA encoding a protein binding to the major histocompatibility complex class II Y box. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[19]  S. Urieli-Shoval,et al.  Defective HLA DRA X box binding in the class II transactive transcription factor mutant 6.1.6 and in cell lines from class II immunodeficient patients. , 1991, Journal of immunology.

[20]  E. Unanue,et al.  α-fetoprotein inhibits macrophage expression of Ia antigens , 1984 .

[21]  P. Stern,et al.  Natural history of HLA expression during tumour development. , 1993, Immunology today.

[22]  P. Stern,et al.  HLA class II antigen expression in human papillomavirus-associated cervical cancer. , 1992, Cancer research.

[23]  M. R. Oliva,et al.  Phenotypic and genetic analysis of HLA class I and HLA-DR antigen expression on human melanomas. , 1988, Experimental and clinical immunogenetics.

[24]  W. Fiers,et al.  Ia expression by vascular endothelium is inducible by activated T cells and by human gamma interferon , 1983, The Journal of experimental medicine.

[25]  A. Concha,et al.  Expression of HLA class I and II antigens in bronchogenic carcinomas: its relationship to cellular DNA content and clinical-pathological parameters. , 1991, Cancer research.

[26]  Peter W. Chen,et al.  Presentation of endogenous tumor antigens to CD4+ T lymphocytes by murine melanoma cells transfected with major histocompatibility complex class II genes , 1994, Journal of leukocyte biology.

[27]  T. Merigan,et al.  Regulation of expression of class II major histocompatibility antigens on human peripheral blood monocytes and Langerhans cells by interferon. , 1984, Human immunology.

[28]  G W Comstock,et al.  Relationship of prediagnostic serum levels of dehydroepiandrosterone and dehydroepiandrosterone sulfate to the risk of developing premenopausal breast cancer. , 1992, Cancer research.

[29]  S. Fuggle,et al.  THE DETAILED DISTRIBUTION OF MHC CLASS II ANTIGENS IN NORMAL HUMAN ORGANS , 1984, Transplantation.

[30]  L. Glimcher,et al.  Sequences and factors: a guide to MHC class-II transcription. , 1992, Annual review of immunology.

[31]  M. Nakanishi,et al.  B-cell-specific and interferon-gamma-inducible regulation of the HLA-DR alpha gene. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[32]  S. Ferrone,et al.  Heterogeneity in the expression of HLA and tumor-associated antigens by surgically removed and cultured breast carcinoma cells. , 1983, Cancer research.

[33]  F. Garrido,et al.  MHC class I and II gene expression on human tumors. , 1988, Advances in experimental medicine and biology.

[34]  M. Greaves,et al.  The presence of HLA-DR antigens on lactating human breast epithelium and milk fat globule membranes. , 1980, Clinical and experimental immunology.

[35]  D J Ruiter,et al.  Phenotypic dynamics of tumor progression in human malignant melanoma , 1985, International journal of cancer.

[36]  M. Greaves,et al.  Differential expression of HLA‐DR and DR‐linked determinants on human leukemias and lymphoid cells , 1983, European journal of immunology.

[37]  P. Möller,et al.  B‐cell lymphomas of high‐grade malignancy frequently lack HLA‐DR, ‐DP and ‐DQ antigens and associated invariant chain , 1987, International journal of cancer.

[38]  L. Glimcher,et al.  Role of lipopolysaccharide and IL-4 in control of transcription of the class II A alpha gene. , 1991, Journal of immunology.

[39]  R. Germain,et al.  Induction of macrophage Ia antigen expression by rIFN-gamma and down-regulation by IFN-alpha/beta and dexamethasone are mediated by changes in steady-state levels of Ia mRNA. , 1987, Journal of immunology.

[40]  G. Wick,et al.  In situ immune complexes, lymphocyte subpopulations, and HLA-DR-positive epithelial cells in Hashimoto thyroiditis. , 1985, Laboratory investigation; a journal of technical methods and pathology.

[41]  F. Garrido,et al.  Class II HLA antigen expression in familial polyposis coli is related to the degree of dysplasia. , 1990, Immunobiology.

[42]  B. Peterlin,et al.  B-cell factor 1 is required for optimal expression of the DRA promoter in B cells , 1992, Molecular and cellular biology.

[43]  F. Garrido,et al.  MHC antigens and malignancy. , 1986, Nature.

[44]  E. Unanue.  Antigen-presenting function of the macrophage. , 1984, Annual review of immunology.

[45]  C. Y. Wang,et al.  Ia-bearing T lymphocytes in man. Their identification and role in the generation of allogeneic helper activity , 1978, The Journal of experimental medicine.

[46]  F. Esteban,et al.  Tumor aggressiveness and MHC class I and II antigens in laryngeal and breast cancer. , 1991, Seminars in cancer biology.

[47]  D. Mason,et al.  Induction of Ia antigen in rat epidermal cells and gut epithelium by immunological stimuli , 1982, The Journal of experimental medicine.

[48]  S. von Kleist,et al.  Lacking prognostic significance of beta 2-microglobulin, MHC class I and class II antigen expression in breast carcinomas. , 1990, British Journal of Cancer.

[49]  N. Hogg,et al.  Association of colorectal tumor epithelium expressing HLA-D/DR with CD8-positive T-cells and mononuclear phagocytes. , 1987, Cancer research.

[50]  J. Johnson,et al.  Expression of HLA-D subloci DR and DQ by breast carcinomas is correlated with distinct parameters of favourable prognois. , 1991, European journal of cancer.

[51]  G. Wong,et al.  Transforming growth factor-beta 1 modulates the expression of class II histocompatibility antigens on human cells. , 1988, Journal of immunology.

[52]  D. Ruiter,et al.  HLA antigen expression in routinely processed head and neck squamous cell carcinoma primary lesions of different sites , 1991, International journal of cancer. Supplement = Journal international du cancer. Supplement.

[53]  L. Ericson,et al.  Non-polarized cell surface expression of HLA-A,B,C and HLA-DR antigens in Graves' thyroid follicle cells. , 1991, Autoimmunity.

[54]  D. Doniach,et al.  ABERRANT EXPRESSION OF HLA-DR ANTIGENS ON BILEDUCT EPITHELIUM IN PRIMARY BILIARY CIRRHOSIS: RELEVANCE TO PATHOGENESIS , 1984, The Lancet.

[55]  E. Unanue,et al.  Prostaglandins modulate macrophage Ia expression , 1982, Nature.

[56]  T. Merigan,et al.  Recombinant gamma interferon differentially regulates class II antigen expression and biosynthesis on cultured normal human keratinocytes. , 1985, Journal of interferon research.

[57]  T. Luger,et al.  Human epidermal cells synthesize HLA-DR alloantigens in vitro upon stimulation with gamma-interferon. , 1985, The Journal of investigative dermatology.

[58]  J. Riley,et al.  Protease treatment of nuclear extracts distinguishes between class II MHC X1 box DNA-binding proteins in wild-type and class II-deficient B cells. , 1993, Journal of immunology.

[59]  A. Aránega,et al.  HLA class I and II expression in rhabdomyosarcomas. , 1991, Immunobiology.

[60]  T. Rognum,et al.  Strong HLA-DR expression in large bowel carcinomas is associated with good prognosis. , 1993, British Journal of Cancer.

[61]  R. Swindell,et al.  Expression of HLA-D Subloci DR and DQ by Breast Carcinomas is Correlated with Distinct Parameters of Favourable Prognosis , 1991 .

[62]  W. Reith,et al.  The DNA-binding defect observed in major histocompatibility complex class II regulatory mutants concerns only one member of a family of complexes binding to the X boxes of class II promoters , 1992, Molecular and cellular biology.

[63]  M. Nakanishi,et al.  Mutational analysis of the DRA promoter: cis-acting sequences and trans-acting factors , 1990, Molecular and cellular biology.

[64]  Smith Me.  MHC antigen expression in colorectal tumours. , 1991 .

[65]  J. Ting,et al.  Regulation of MHC gene expression. , 1993, Current opinion in immunology.

[66]  D. R. Gamble,et al.  In situ characterization of autoimmune phenomena and expression of HLA molecules in the pancreas in diabetic insulitis. , 1985, The New England journal of medicine.

[67]  S. Pizzo,et al.  Modulation of mouse peritoneal macrophage Ia and human peritoneal macrophage HLA-DR expression by alpha 2-macroglobulin "fast" forms. , 1987, Journal of immunology.

[68]  T. Luger,et al.  Human Epidermal Cells Synthesize HLA-DR Alloantigens In Vitro upon Stimulation with γ-Interferon , 1985 .

[69]  H. Whitwell,et al.  Distribution of histocompatibility and leucocyte differentiation antigens in normal human colon and in benign and malignant colonic neoplasms. , 1984, British Journal of Cancer.

[70]  H. Drexhage,et al.  Dendritic cells in autoimmune thyroid disease. , 1987, Acta endocrinologica. Supplementum.

[71]  C. Janeway,et al.  Quantitative variation in la antigen expression plays a central role in immune regulation. , 1984, Immunology today.

[72]  G. Kroemer,et al.  Mechanisms of self tolerance. , 1992, Immunology today.

[73]  A. Siddiqui,et al.  Trans-activation of HLA-DR gene by hepatitis B virus X gene product. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[74]  M. R. Oliva,et al.  HLA molecules in basal cell carcinoma of the skin. , 1992, Immunobiology.

[75]  J. Ting,et al.  Upstream DNA sequences required for tissue-specific expression of the HLA-DR alpha gene. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[76]  A. Foulis,et al.  Aberrant Expression of HLA-DR Antigens by Insulin-Containing β-Cells in Recent-Onset Type I Diabetes MelIitus , 1986, Diabetes.

[77]  R. Winchester,et al.  Recognition by pregnancy serums of non-HL-A alloantigens selectively expressed on B lymphocytes , 1975, The Journal of experimental medicine.

[78]  T. Chang,et al.  Cellular origin and interactions involved in gamma-interferon production induced by OKt3 monoclonal antibody. , 1982, Journal of immunology.

[79]  F. Garrido,et al.  MHC expression on human tumors--its relevance for local tumor growth and metastasis. , 1991, Seminars in cancer biology.

[80]  A. Floreani,et al.  Progression of autoimmune damage in primary biliary cirrhosis: an immunohistochemical study. , 1989, Autoimmunity.

[81]  K. Koretz,et al.  Frequency of abnormal expression of HLA‐A,B,C and HLA‐DR molecules, invariant chain, and LFA‐3 (CD58) in colorectal carcinoma and its impact on tumor recurrence , 1991, International journal of cancer. Supplement = Journal international du cancer. Supplement.

[82]  D. Mason.  The Possible Role of Class II Major Histocompatibility Complex Antigens in Self Tolerance , 1985, Scandinavian journal of immunology.

[83]  G. Canonica,et al.  Expression of intercellular adhesion molecule‐1 (ICAM‐1) on thyroid epithelial cells in Hashimoto's thyroiditis but not in Graves' disease or papillary thyroid cancer , 1991, Clinical and experimental immunology.

[84]  K. West,et al.  An evaluation of the prognostic significance of HLA‐DR expression in gastric carcinoma , 1990, Cancer.

[85]  T. Mattfeldt,et al.  Expression of HLA-A, -B, -C, -DR, -DP, -DQ, and of HLA-D-associated invariant chain (Ii) in non-neoplastic mammary epithelium, fibroadenoma, adenoma, and carcinoma of the breast. , 1989, The American journal of pathology.

[86]  E. Shevach,et al.  FUNCTION OF MACROPHAGES IN ANTIGEN RECOGNITION BY GUINEA PIG T LYMPHOCYTES , 1973, The Journal of experimental medicine.

[87]  A. Houghton,et al.  Class II histocompatibility antigen expression in human melanocytes transformed by Harvey murine sarcoma virus (Ha-MSV) and Kirsten MSV retroviruses , 1986, The Journal of experimental medicine.

[88]  M. Smith.  MHC antigen expression in colorectal tumours. , 1991, Seminars in cancer biology.

[89]  E. Thorsby,et al.  Complement and cell-mediated specific destruction of human endothelial cells treated with anti-DRw antisera. , 1979, Transplantation Proceedings.

[90]  V. Quaranta,et al.  EXPRESSION OF Ia‐LIKE ANTIGENS IN NORMAL HUMAN NONLYMPHOID TISSUES , 1981, Transplantation.