Tumour MHC class I downregulation and immunotherapy (Review).
MHC class I downregulation is an important mechanism of tumour escape from T cell-mediated immune responses. Approximately 40-90% of human tumours derived from various MHC class I+ tissues were reported to be MHC class I deficient. Decreased or absent MHC class I expression is frequently associated with the invasive and metastatic tumour phenotype. Altered MHC class I antigen expression involves total loss, loss of haplotype, locus downregulation, allelic loss or downregulation, and combinations. Description of partial or complete losses of MHC class I molecules in tumour cells as mechanisms of immune escape often fails to consider an increased susceptibility to NK cell-mediated lysis, which is a direct consequence of such losses. A low MHC class I level favours NK cells as effectors, whereas a high level of MHC class I favours T cells as effectors. The microheterogeneity of MHC class I expression in tumour cell populations, the balance of the MHC-restricted and MHC-unrestricted defence as well as the selective pressure of antigen-specific (CTL) and antigen non-specific (NK) effector mechanisms decide the final outcome of the MHC class I expression in the primary tumour and its metastases as well as the final outcome of the tumour defence reaction. Despite the MHC class I molecule deficiency and the resulting absence of the CD8+ T cell-mediated immunity, the tumour hosts were found to be capable of being immunized against MHC class I- tumours. The purpose of this review is to discuss the positive results of MHC class I- tumour treatment obtained with immunomodulatory cytokines and tumour vaccines, as well as the prospects and limitations of such therapy.
Bubeník
Jan
J
Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, 166 37 Prague 6, Czech Republic. bubenik@img.cas.cz
D000483:Alleles; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D015536:Down-Regulation; D006239:Haplotypes; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007694:Killer Cells, Natural / Q000166:cytology; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D010641:Phenotype
D015395:Histocompatibility Antigens Class I