The immune system is built up to identify and battle what might be dangerous (e.g., virus, bacteria, exogenous proteins) for the organism. Innate and adaptive immune responses tightly co-operate at this task usually with excellent results. Is a tumor cell considered an “enemy” by the immune system? Indeed, tumor cells possess antigens (i.e. signals detected by the cells of the immune system), which might trigger an immune response. In vitro and in animal models is rather simple to demonstrate that tumor cells are recognized and eliminated by the immune system, and T lymphocytes, the effectors of the adaptive immune response, appear to play the most relevant role. However, spontaneous rejection of measurable tumors rarely occurs in humans. Which are therefore, the rules governing the interactions among a growing tumor, its surrounding stroma and the immune system? Major goal of our research is to achieve a deeper understanding of the molecular events regulating the interactions among transformed cells, their surrounding stroma and the immune system during the different phases of tumor development and progression. This knowledge is then implemented to identify means whereby induce in vivo a therapeutic tumor-specific immune response. Final goal is to translate the most promising among these novel therapies into clinical trials.