Linking metabolism and anti-cancer functions of dendritic cells
Stefanie K. Wculek
IRB and BIST, Barcelona
Dendritic cells are fundamental to induce adaptive CD4+ and CD8+ T cell responses against cancer. We find that conventional type 1 (cDC1) and type 2 (cDC2) dendritic cell subsets have a distinct potential to control cancer progression upon adoptive transfer (DC vaccination) in mouse models. cDC1s excel at priming of resident-memory CD4+ helper T cells (Trm) and memory CD8+ T cells that prevent experimental cancer relapse. Notably, the intratumoral abundance of cDC1-induced CD4+ Trm correlates with improved survival of cancer patients. We also discovered a differential bioenergetic dependence of the immunogenic responsiveness of cDC1s versus cDC2s. High mitochondrial respiration regulates the epigenetic state and rapid functional outputs of cDC1s, which is vital for their potency to induce anti-cancer immunity. Overall, I will present unpublished data on novel functions of dendritic cells in cancer
and their metabolic regulation.