Analyses for the establishment of the effective immunotherapy to melanoma-bearing hosts

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We revealed that STAT3-restricted cytokines, especially IL-6 from B16 melanoma cells suppressed IFN-gamma-production in both CD4+ and CD8+ T-cells. In culture, IL-6 from B16 cells was reduced by pretreatment with rR9-GRIM19. In vivo, although intratumoral injections of rR9-GRIM19 elicited anti-B16 effects with frequencies of IL-6-producing T-cell phenotypes, complete B16 regression was not observed. To elicit complete B16 regression, we investigated the antitumor effects of combination immunotherapies with rR9-GRIM19. rR9-GRIM19 elicited enhanced antitumor effects when combined either with rR9-OVA or CpG-ODN, but only the combination of CpG-ODN, rR9-OVA, and rR9-GRIM19 (COG therapy) elicited complete B16 tumor regression. Interestingly, melanoma-specific cytotoxic T lymphocyte (CTL) expansion with IFN production occurred in COG-treated B16-bearing. We finally confirmed that rIFN exposure could significantly enhance rR9-GRIM19-treated anti-B16 melanoma effects in vitro and in vivo.