Abstract 3176: Linking suppressive activity and ER-Stress in Myeloid Derived Suppressor Cells

In recent years, immunotherapies have shown great promise for the treatment of cancer patients. However, the presence of a very potent immunosuppressive microenvironment in the tumor site remains one of the major obstacles in fully harnessing the potential of immunotherapeutic strategies. Myeloid Derived Suppressor cells (MDSC) represent one of the main suppressive populations inside the tumor. These cells can be divided in two sub-populations: PMN-MDSC and Monocytic-MDSC. They suppress immune response using various well-known mechanisms and accumulate to a large extent in tumor-bearing hosts. Despite the increasing body of literature on MDSC, which mechanisms drives their suppressive capacity remains unclear. Our group recently reported that the ER-Stress response is activated in MDSC isolated from tumor bearing mice and cancer patients. In this study, we investigated the possibility that the ER-stress response could be responsible for the immune suppressive capacities of MDSC. To test this hypothesis, we induce ER-Stress using well-known chemical inducer into non suppressive myeloid cells (PMN and monocyte) and assess their ability to suppress T cells function. Our results show that, following ER-Stress induction, normal myeloid cells were able to suppress T cells response (in murine and human system). To better understand how the ER-Stress response can induce suppressive capacities, we performed microarray analysis following treatment with ER-Stress inducer. Interestingly, we found that arginase-1, one the major enzyme implicated in MDSC suppressive capacities, was induced by more than 5 fold. Altogether, our results suggest that activation of the ER-Stress response in MDSC could be responsible for the up-regulation of arginase-1 and the suppressive phenotype of MDSC. These results suggest that targeting the ER-Stress response in cancer patients could inhibit the suppressive activity of MDSC and improve the efficacy of current immunotherapies. Citation Format: Thomas C. Condamine, Vinit Kumar, Dmitry I. Gabrilovich. Linking suppressive activity and ER-Stress in Myeloid Derived Suppressor Cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3176. doi:10.1158/1538-7445.AM2015-3176