Tumor Associated Mitochondria Antigens (TAMAs) vaccine is effective on tumor and tumor associated endothelial cells: from the mechanisms to the clinical validation 3298

Abstract Description A major challenge for immunotherapy is the scarcity of effective cancer-specific antigens. Somatic mitochondrial (mt)DNA mutations can lead to Tumor Associate Mitochondria Antigens (TAMAs). Our group developed an effective antitumor dendritic cells based vaccine using mt lysates from renal cell carcinoma, harboring immunogenic mtDNA mutations, and we used it in combination with αPDL-1. The combination of therapies improves tumor control compared to single therapy and increases survival rate augmenting infiltration and reactivity of T cells. Interestingly, the combination of treatments favors tumor vessel normalization, which benefits tumor blood perfusion and decreases hypoxia enhancing reactive T cells infiltration, thereby boosting the efficacy of the TAMAs vaccine. Since we detected a correlation between CD8 cells infiltrating tumor and apoptosis of tumor vessel, we showed that endothelial cells that have naturally internalized tumor mitochondria, and hence TAMAs, are recognized by primed TAMAs T cells, which promote vessel pruning. To validate the translational relevance of the study, we demonstrated the immunogenicity of TAMAs in human healthy donors and the impact on tumor vasculature in patients harboring mt immunogenic mutations. In conclusion, we validate the immunogenicity of TAMAs in human and unveil a new immunological mechanism of tumor vasculature pruning opening a new strategy that could improve cancer therapies targeting both cancer and vasculature. Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)