The selection of tumor variants with altered expression of classical and nonclassical MHC class I molecules: implications for tumor immune escape.
Tumor immune escape variants can be identified in human and experimental tumors. A variety of different strategies are used by tumor cells to avoid recognition by different immune effector mechanisms. Among these escape routes, alteration of MHC class I cell surface expression is one of the mechanisms most widely used by tumor cells. In this review we focus our attention on the T-cell immune selection of MHC class I-deficient tumor variants. Different altered MHC class I phenotypes that originate from multiple molecular mechanisms can be identified in human tumors. MHC-deficient tumor clones can escape T-cell immune responses, but are in theory more susceptible to NK-cell-mediated lysis. In this context, we also review the controversial issue of the aberrant expression of nonclassical HLA class I molecules, particularly HLA-G, in tumors. This expression may be relevant in tumor cells that have lost the capacity to interact with NK inhibitory receptors-namely, those tumor cells with no HLA-B or HLA-C expression. Most published studies have not analyzed these possibilities and do not provide information about the complete HLA-A, HLA-B, or HLA-C molecule profiles of the tumors studied. In contrast, HLA-E has been reported to be expressed in some tumor cell lines with very low HLA-A, HLA-B, and HLA-C expression, suggesting that HLA-E may indeed, in some cases, play a role by inhibiting NK lysis of cells that otherwise would be destroyed by NK cells. Finally, we provide evidence that the status of the immune system in the tumor-bearing animal is capable of defining the MHC profile of the tumor cells. In other words, MHC class I-negative metastatic colonies are produced in immunocompetent animals, and MHC class I-positive colonies in T-cell immunodeficient individuals.
Algarra
Ignacio
I
Departamento de Ciencias de La Salud, Universidad de Jaén, Spain.
García-Lora
Angel
A
Cabrera
Teresa
T
Ruiz-Cabello
Francisco
F
Garrido
Federico
F
D000818:Animals; D000940:Antigenic Variation; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D002999:Clone Cells / Q000473:pathology; D005805:Genes, MHC Class I; D006183:H-2 Antigens / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000276:immunology*; D006801:Humans; D007157:Immunologic Surveillance; D051379:Mice; D018345:Mice, Knockout; D008819:Mice, Nude; D018448:Models, Immunological; D009369:Neoplasms / Q000276:immunology*; D012641:Selection, Genetic; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019139:Tumor Escape / Q000276:immunology*; D000097625:HLA-E Antigens
D000951:Antigens, Neoplasm; D006183:H-2 Antigens; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D000097625:HLA-E Antigens