1262 Immuno-apoptotic priming to enhance the efficacy of immunotherapies in melanoma

Melanoma remains a significant and rising health burden. Currently most melanoma patients are treated with immunotherapies, but almost half do not respond to, or relapse from the treatments. One of main contributors to immunotherapy resistance is an immunosuppressive cell population, called myeloid-derived suppressive cells (MDSCs). Therefore, enhancing efficacy immunotherapies by targeting MDSCs represents promising strategy improve overall outcomes. unexplored mechanism regulating tumor immune survival using BH3 mimetics. mimetics small molecule therapies that block anti-apoptotic function BCL2 family proteins in cancer cells, resulting death. MCL1 pro-survival member family. Our recent study suggests such as inhibitor (MCL1i) can induce apoptosis uveal vitro vivo. This aimed investigate how MCL1i influence immunotherapy. We examined transcriptional profile tumor-associated myeloid two who relapsed anti-PD1 treatment single-cell RNA-sequencing. found displayed excessive expression, suggesting inhibiting may be rational target immunotherapies. To test this possibility, we effects syngeneic model B16 mouse line immunocompetent C57B6 mice. decreased frequency infiltrating MDSCs, while increasing activation CD8+ T cells. Further, enhanced anti-PD-1 combination significantly delayed growth compared either single drug treatment. Taken together, indicates candidates for melanoma.