Our objective is to identify mechanisms involved in immune subversion by cancer cells and to develop therapeutic strategies based on the immunogenicity of tumor cell death and reactivation of immune-surveillance. The tumor models we use are breast and ovarian carcinoma and sarcoma, in which molecular characterization is advanced (leading to the identification of new molecular types), and in which therapy targeted on oncogene showed their first successes. Since 2005, our project has involved two approaches: i) the identification of the immunosuppressive mechanisms induced by tumors, and ii) the characterisation of new mutations driving cancer with the aim to develop cytotoxic therapies specifically targeted on oncogenes combined with an immunotherapy strategy. In clinical terms, it is also fundamental to eradicate cancer stem cells (CaSC), also named Tumor-Initiating Cells, as likely involved in resistance and relapse in cancers. Thus, we will determine some therapeutic combinations able to induce an anti-tumor response with a long term memory in order to prevent relapse and eradicate cancer stem cells.