Rho GTPases inhibitors and IFN-γ treatment stimulates anti-melanoma immune response

The lack of MIIC class I (MIIC-I) and costimulatory molecules on tumor cells resutls in inefficient stimulation of tumor-reactive T lymphocytes. The costimulatory signal can be provided by members of the TNT/TNFR super family which are expressed on the T-cell membrane. Stably transfected murine melanoma cells, expressing CD101, CD70 and MHC-I molecules enhanced the immune anti-tumor response and favour a long-lasting immune memory [1]. These observations suggest that new immunotherapeutic protocols, using melanoma cells expressing MHC-I and costimulatory molecules can be conceivable. Consequently, we investigated drugs which could enhacne expression of costimulatory and MHC-I complexes on melanoma cells. We showed that Tho GTPases inhibitors could be good candidates [2]. Indeed, in vitro treatments with IFN-gamma and Rho GTPases inhibitors are able to stimulate membrane expression of enstimulatory and MHC-I molecules on murine and human melanoma cell lines. Furthermore, used as stimulator cells these treated melanoma cells favour the proliferation of specific CD8 T lymphocytes and in vivo and the reduction of the tumor growth.