IL-12 directly up-regulates the expression of HLA class I, HLA class II and ICAM-1 on human melanoma cells: a mechanism for its antitumor activity?

IL-12 enhances cytolytic activity and proliferation of NK and T cells, and induces cytokines such as IFN-gamma. No direct effects on non-hematopoietic cells have been shown. This study investigates the effects of IL-12 on mel anoma cells in vitro. We analyzed 15 melanoma cell cultures and 1 melanoma cell line. Out of 16 samples 13 expressed the beta chain of the IL-12 recep tor (IL-12R beta). Preincubation with IL-12 increased the surface levels of human leukocyte antigen (HLA) class I, HLA class II and intercellular adhe sion molecule (ICAM)-1 of those cultures with IL-12R beta expression. The e ffects of IL-12 on HLA class I could be blocked by an IL-12-neutralizing mo noclonal antibody (mAb), but not by an mAb against IFN-gamma. Melanoma cell s transduced with IL-12 expressed enhanced levels of HLA class I, HLA class II and ICAM-1 compared to controls. Co-incubation of the melanoma cells wi th allogeneic peripheral blood mononuclear cells (PBMC) resulted in enhance d proliferation and increased production of IL-2 and IFN-gamma after pretre atment with IL-12. IL-12 pretreatment increased the susceptibility of melan oma cells to lysis by prestimulated autologous PBMC. Since IL-12 induced im munocritical surface molecules on melanoma cells, it might be beneficial du ring immune interventions in melanoma patients.