The immune system may combat and prevent the development of tumor cells. However, during the many stages of tumorigenesis, tumor cells progressively lose their immunogenicity and become less susceptible to anti-tumor immune mechanisms. Furthermore, the immunosuppressive tumor environment can reverse these mechanisms and make this system work in favor of tumor cells. Thus, the restoration of the immune system can be considered as a determining factor for the success of cancer treatment. Among the methods that can be used for this purpose, the combination of cancer immunotherapy with chemotherapy can be considered as an interesting strategy. Because, at the same time, such association can activate an immune response, reduce the immunosuppressive mechanisms and enhance the susceptibility of tumor cells to immune attack. Data from our laboratory also show a synergistic effect between these therapies. First, we have demonstrated that the gene transfer of p19Arf (tumor suppressor protein) and Interferon-beta (IFN², immunomodulatory cytokine) mediated by adenovirus induces cell death and an antitumor immune response against a secondary challenge. Then, the combination of these vectors was used as immunotherapy prior to treatment with the chemotherapeutic agent cisplatin, resulting in a dramatic reduction of tumor progression compared to the individual therapies. Although this favorable response in the presence of both therapies, cisplatin does not induce immunogenic cell death (a strong immune antitumor activity mediated by dendritic cells and CD4 + and CD8 + cells). Thus, with the purpose of enhancing the antitumor immune response, it iwould interesting to associate the immunotherapy mediated by the gene transfer of p19Arf/IFN² with the immunogenic cell death induced by chemotherapeutic doxorubicin. We hypothesize that the immunostimulatory effects of the immunotherapy p19Arf/IFN² and the immunogenic cell death acts synergistically on the immune system, modulate the immunosuppression caused by the tumor microenvironment and favor the treatment of cancer.
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