Chemo-immunotherapy The overall goal is to improve the outcome of mesothelioma by combining conventional chemotherapy with immunotherapy in murine mesothelioma models.
Although the first line chemotherapy composed of cisplatin and Pemetrexed (Alimta) could prolong survival compared with cisplatin alone, the effect is limited. One neglected issue that has been highlighted is cancer cell repopulation during the intervals of chemotherapy. Evidence has shown that the rate of repopulation of surviving cancer cells accelerates over time. Therefore, novel approaches inhibiting this process need to be developed. The immune suppression is quite common in cancer microenvironment including mesothelioma. We attempt to improve the efficacy of chemotherapy by removing the brake of immunosuppression so as to enhance specific anti-tumor immunity. The immunosuppressive compartments such as regulatory T cells (Treg), CTLA-4, PD-1 and so on can be employed as targets to enhance T cell immune response.
We have demonstrated that Treg cell depletion between cycles of chemotherapy has resulted in improvement of the anti-tumor effect. CTLA-4 blockade expands infiltrating T cells and inhibits cancer cell repopulation between chemotherapy treatments in murine mesothelioma models.