Interferon-gamma treatment of B16 melanoma cells: opposing effects for non-adaptive and adaptive immune defense and its reflection by metastatic spread.
The impact of interferon-gamma (IFN) treatment of tumor cells on non-adaptive and adaptive immune defense and its reflection by metastatic spread were evaluated using a weakly metastasizing variant of B16 melanoma (B16-FI). Treatment of B16-FI with IFN resulted in a decrease in binding structures for NK cells and concomitantly in augmented metastasizing capacity. In line with this, activation of NK cells and Mo, which led to reduction of metastatic nodes, was less efficient with IFN-treated B16-FI, while after elimination of non-adaptive immune defense, the number of metastases increased significantly, but irrespective of IFN treatment. On the other hand, IFN-treated B16-FI cells become more prone to killing by cytotoxic T-cells (CTL). This was due to increased lysability by CTL and to increased immunogenicity; i.e., a higher frequency of B16-specific CTL was observed after immunization with IFN-treated than with untreated B16-FI. The reverse phenomenon was observed with anomalous and/or lymphokine-activated killer cells (AK/LAK). The common cause of increased antigenicity and immunogenicity may reside in increased expression of class-I and de novo expression of class-II MHC antigens after IFN treatment. Increased antigenicity and immunogenicity of IFN-treated B16-FI was reflected by significant reduction of metastatic nodes, prolonged survival and increased TD100 in animals immunized with IFN-treated vs. untreated melanoma cells. Comparison of the divergent effects of IFN treatment on B16-FI melanoma cells showed that the benefit of increased antigenicity/immunogenicity clearly outweighed the disadvantage of reduced susceptibility to non-adaptive immune defense.
D000818:Animals; D002460:Cell Line; D007111:Immunity, Cellular / Q000187:drug effects; D007371:Interferon-gamma / Q000494:pharmacology* / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000276:immunology*; D008175:Lung Neoplasms / Q000556:secondary*; D008285:Major Histocompatibility Complex / Q000187:drug effects; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology
D007371:Interferon-gamma