Molecular mechanisms used by tumors to escape immune recognition: immunogenetherapy and the cell biology of major histocompatibility complex class I.

In this article, we explore the hypothesis that tumor cells can escape recognition by CD8+ T cells via deficiencies in antigen processing and presentation. Aspects of the molecular and cellular biology of major histocompatibility complex class I are reviewed. Evidence for histology-specific molecular mechanisms in the antigen-processing and -presentation deficiencies observed in some human and murine tumors is presented. Mechanisms identified include down-regulation of antigen processing, loss of functional beta 2-microglobulin, and deletion of specific alpha-chain alleles. Finally, we discuss studies using an antigen-presentation-deficient mouse tumor as a model for the immunogenetherapy of an antigen-presentation deficiency.

[1]  M. Herlyn,et al.  Melanoma cells and normal melanocytes share antigens recognized by HLA- A2-restricted cytotoxic T cell clones from melanoma patients , 1993, The Journal of experimental medicine.

[2]  E. Gilboa,et al.  Antimetastatic vaccination of tumor-bearing mice with two types of IFN-gamma gene-inserted tumor cells. , 1993, Journal of immunology.

[3]  J. Yewdell,et al.  Identification of human cancers deficient in antigen processing , 1993, The Journal of experimental medicine.

[4]  P. Cresswell,et al.  Proteasome subunits encoded in the MHC are not generally required for the processing of peptides bound by MHC class I molecules , 1992, Nature.

[5]  J. Neefjes,et al.  Proteasome subunits encoded by the major histocompatibility complex are not essential for antigen presentation , 1992, Nature.

[6]  Kathleen R. Cho,et al.  Genetic alterations in the adenoma–carcinoma sequence , 1992, Cancer.

[7]  S. Rosenberg,et al.  A nonimmunogenic sarcoma transduced with the cDNA for interferon gamma elicits CD8+ T cells against the wild-type tumor: correlation with antigen presentation capability , 1992, The Journal of experimental medicine.

[8]  J. Monaco,et al.  A molecular model of MHC class-I-restricted antigen processing. , 1992, Immunology today.

[9]  J. Yewdell,et al.  Cell biology of antigen processing and presentation to major histocompatibility complex class I molecule-restricted T lymphocytes. , 1992, Advances in immunology.

[10]  P. Chomez,et al.  A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. , 1991, Science.

[11]  R. Coffman,et al.  Role of Cytokines in the Differentiation of CD4+ T‐Cell Subsets in vivo , 1991, Immunological reviews.

[12]  A. Asher,et al.  Defective presentation of endogenous antigens by a murine sarcoma. Implications for the failure of an anti-tumor immune response. , 1991, Journal of immunology.

[13]  H. Rammensee,et al.  Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules , 1991, Nature.

[14]  S. Rosenberg,et al.  Interferon gamma and tumor necrosis factor have a role in tumor regressions mediated by murine CD8+ tumor-infiltrating lymphocytes , 1991, The Journal of experimental medicine.

[15]  J. Ragoussis,et al.  Map of the human MHC. , 1991, Immunology today.

[16]  P. Greenberg.  Adoptive T cell therapy of tumors: mechanisms operative in the recognition and elimination of tumor cells. , 1991, Advances in immunology.

[17]  S. Ferrone,et al.  Lack of HLA class I antigen expression by cultured melanoma cells FO-1 due to a defect in B2m gene expression. , 1991, The Journal of clinical investigation.

[18]  E. Gilboa,et al.  Retroviral vector-mediated gamma-interferon gene transfer into tumor cells generates potent and long lasting antitumor immunity. , 1990, Cancer research.

[19]  Hans-Georg Rammensee,et al.  Isolation and analysis of naturally processed viral peptides as recognized by cytotoxic T cells , 1990, Nature.

[20]  P. Cresswell,et al.  Presentation of viral antigen controlled by a gene in the major histocompatibility complex , 1990, Nature.

[21]  M. Bevan,et al.  Defective presentation of endogenous antigen by a cell line expressing class I molecules. , 1990, Science.

[22]  H. Rammensee,et al.  Limit of T cell tolerance to self proteins by peptide presentation. , 1990, Science.

[23]  H. Ljunggren,et al.  In search of the 'missing self': MHC molecules and NK cell recognition. , 1990, Immunology today.

[24]  H. Ananthaswamy,et al.  Afferent and efferent specificity in the induction and elicitation of parental cross-protective immunity by an immunogenic murine tumor variant: associative recognition of a unique tumor-specific antigen on somatic cell hybrids. , 1989, Cancer research.

[25]  H. Ljunggren,et al.  Association of class I major histocompatibility heavy and light chains induced by viral peptides , 1989, Nature.

[26]  A. Townsend,et al.  Antigen recognition by class I-restricted T lymphocytes. , 1989, Annual review of immunology.

[27]  S. Rosenberg,et al.  Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report. , 1988, The New England journal of medicine.

[28]  H. Schreiber,et al.  Unique tumor-specific antigens. , 1988, Annual review of immunology.

[29]  J. Levin,et al.  Synthesis and cellular location of the ten influenza polypeptides individually expressed by recombinant vaccinia viruses. , 1987, Virology.

[30]  S. Rosenberg,et al.  Identification of cellular mechanisms operational in vivo during the regression of established pulmonary metastases by the systemic administration of high-dose recombinant interleukin 2. , 1987, Journal of immunology.

[31]  S. Rosenberg,et al.  A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes. , 1986, Science.

[32]  J. Minna,et al.  Markedly decreased expression of class I histocompatibility antigens, protein, and mRNA in human small-cell lung cancer , 1985, The Journal of experimental medicine.

[33]  J. Yagüe,et al.  Primary structure of human T-cell receptor α-chain , 1984, Nature.