Abstract IA35: Determinants of effective tumor immunity

Treatment of solid tumors has been revolutionized by immune checkpoint blockade therapies; yet even for melanoma, for which high response rates are observed, the majority of tumors continue to grow after therapy. To identify immune cell states associated with success or failure of immunotherapy, we profiled the single-cell transcriptomes of immune cells from tumor samples obtained from melanoma patients treated with checkpoint inhibitors. We defined specific activation states of CD8+ T cells that associate with tumor growth post-therapy, delineated their epigenetic landscape and clonality, and demonstrated enhanced immunity by targeting a novel combination of T cell factors. We also found that expression of a single T cell gene was predictive of tumor regression in response to therapy. Our study thus reveals immune cell states and molecules that help explain effective immunotherapy in humans. Citation Format: Nir Hacohen. Determinants of effective tumor immunity [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr IA35.