title: MHC antigen expression by melanomas recovered from mice treated with allogeneic mouse fibroblasts genetically modified for interleukin-2 secretion and the expression of melanoma-associated antigens.
abstract: Recent approaches toward the immunotherapy of neoplastic disease involve the introduction of expression-competent genes for interleukin-2 (IL-2) into autologous malignant cells. Treatment of tumor-bearing experimental animals with the IL-2-secreting cells successfully induces partial and at times complete remissions. In most instances, however, although delayed, progressive tumor growth continues. Here, certain of the characteristics of B16 melanomas (H-2b) persisting in C57BL/6 mice (H-2b) treated with an IL-2-secreting, melanoma-antigen-positive cellular immunogen (RLBA-IL-2 cells) are described. Unlike the melanoma cells first injected, B16 cells recovered from mice treated with RLBA-IL-2 cells were deficient in the expression of MHC class I, but not class II determinants. Deficient MHC class I expression correlated with the cells' resistance to cytotoxic T lymphocytes (CTL) from the spleens of mice immunized with RLBA-IL-2 cells. Melanomas persisting in mice treated with non-IL-2-secreting, melanoma-antigen-positive cell constructs (RLBA-ZipNeo cells) were also deficient in the expression of MHC class I determinants, and the melanoma cells were resistant to CTL from mice immunized with RLBA-ZipNeo cells. Thus, the expression of melanoma-associated antigens rather than IL-2-secretion correlated with deficient MHC class I expression by the persistent melanomas. This point was substantiated by the expression of MHC class I antigens by melanomas persisting in mice treated with IL-2-secreting, melanoma-antigen-negative LM cells (LM-IL-2); it was equivalent to that of melanomas in untreated mice. The involvement of MHC class I antigens in the immune resistance of persistent melanoma cells from mice treated with the melanoma-antigen-positive immunogens was indicated by the effect of interferon gamma (IFN gamma) or N-methyl-N'-nitro- N-nitrosoguanidine (MNNG) on the susceptibility of the cells to anti-melanoma CTL. Treatment of the resistant melanomas with IFN gamma or MNNG stimulated MHC class I antigen expression and restored the cells' sensitivity to CTL from mice immunized with IL-2-secreting or nonsecreting, melanoma-antigen-positive cellular immunogens. Prior treatment of the treated cells with antibodies to MHC class I determinants inhibited the cells' susceptibility to CTL from mice immunized with RLBA-IL-2 cells.
authors.affiliation: Department of Microbiology and Immunology, University of Illinois College of Medicine, Chicago 60612.
authors.forename: T S
authors.initials: TS
authors.lastname: Kim
authors.forename: E P
authors.initials: EP
authors.lastname: Cohen
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005260:Female; D006183:H-2 Antigens / Q000276:immunology*; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000276:immunology*; D008546:Melanoma, Experimental / Q000276:immunology*; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000276:immunology; D013154:Spleen / Q000166:cytology; D014162:Transfection
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D006183:H-2 Antigens; D007376:Interleukin-2; D009363:Neoplasm Proteins; D008769:Methylnitronitrosoguanidine; D007371:Interferon-gamma