title: IFN-treatment of B16-F1 versus B16-F10: relative impact on non-adaptive and T-cell-mediated immune defense in metastatic spread.
abstract: Treatment of tumor cells with interferon-gamma (IFN) frequently reduces their susceptibility towards NK cells and results in augmented expression of MHC antigens, which may increase immunogenicity of tumor cells. Depending on the relative strength of these opposing effects, i.e. escape from non-adaptive immune defense versus facilitated activation of T-cell-mediated defense, IFN-treatment may be beneficial or disadvantageous for the tumor-bearing host. This is demonstrated for the variants F1 and F10 of the B16 melanoma, which differ in metastasizing capacity. IFN-treatment of B16-F1 melanoma cells significantly reduced susceptibility towards non-adaptive immune defense, and increased metastasizing potential. On the other hand, H2K antigen expression was augmented by a factor of 50; concomitantly, lysability by CTL was increased, together with the number and expansion rate of cytotoxic T-cell precursors (CTLp) recruited after immunization with IFN-treated B16-F1. The benefit of increased antigenicity and immunogenicity outweighed the disadvantage or reduced susceptibility towards non-adaptive immune defense. B16-F10 cells were less susceptible to NK cells, expression of MHC antigens was found to be stronger and they were more immunogenic than B16-F1 cells. After IFN-treatment, susceptibility to non-adaptive immune defense was further reduced. Expression of MHC antigens as well as antigenicity and immunogenicity were only moderately augmented. As a consequence, the decreased susceptibility to non-adaptive immune defense was dominating in the tumor bearing host and could not be counterbalanced by immunization with IFN-treated B16-F10 cells. We interpret these data to show that a precise knowledge of the relative decrease in susceptibility to non-adaptive immune defense, the relative increase in MHC antigen expression, antigenicity and immunogenicity may allow a more precise prognosis of the influence of IFN on metastatic capacity in the B16 system, and eventually also in a clinical therapeutic regimen.
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D006183:H-2 Antigens / Q000276:immunology; D007113:Immunity, Innate; D007114:Immunization; D007371:Interferon-gamma / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000556:secondary; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000473:pathology; D051379:Mice; D009362:Neoplasm Metastasis / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D006183:H-2 Antigens; D007371:Interferon-gamma