Adoptively transferred naïve CD8 T cells develop enhanced effector function and improved persistence in neoantigen tumors 4282

Abstract Description We found that naïve antigen specific CD8 T cells regress neoantigen tumors to a much greater extent than wild-type melanoma tumors and wanted to further explore both the kinetics of the adoptively transferred cells and mechanisms important in this therapy. To examine this, we utilized the pmel-1 transgenic model in which CD8 T cells express a TCR recognizing melanoma antigen, gp100, as well as two different tumor lines – B16F10 (wild-type tumors) or the mutated B16KVP (neoantigen tumors). Transferred pmel-1 T cells led to long-term cures and protection from tumor rechallenge only in mice given neoantigen tumors. Additionally, using Nanostring, we detected enhanced interferon signaling, immune effector processes, and chemokine activity in the neoantigen compared to wild-type tumored mice given adoptive T cell therapy (ACT). Cytokine profiling also revealed an increase in several inflammatory cytokines in the neoantigen versus wild-type tumored mice given ACT. Next, we assessed the kinetics of the transferred cells and found that they traffic to the lymph node (LN) early on before reaching the tumor on day 3 post-ACT. Yet, they only persist and adopt an effector phenotype (CD44+ CD62L-) in mice with neoantigen tumors, and blocking LN trafficking diminishes this response in these mice. In summary, neoantigen tumors uniquely allow transferred CD8 T cells to mediate enhanced effector function and persistence. Funding Sources This work was supported by the Melanoma Research Foundation (to MCW), NCI T32 CA272392-01A1 (to MCW), NCI F31CA281258-01A1 (to ACC), ARCs Foundation (to ACC), NCI R01CA287866-01, R01CA275199-02, V Foundation, plus MUSC and Emory University Start Up Funds (to CP). Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)