Aging evokes immunosuppressive CD8+ T cells actively to support cancer
Age-associated dysregulation and exhaustion of CD8+T cells is thought to impair antitumor responses and thus, increase cancer. Here we present evidence that CD8+T cells also actively promote tumor progression with age. We find that aging induces an expansion of a unique population of CXCR6+CD101+CD8+T cells expressing ectonucleotidases CD39 and CD73 (termed DP8 cells) via B cells presenting cognate antigen. We show that progressive (but not regressive) tumors in aged mice recruit these DP8 cells by expressing CXCL16 to suppress antitumor effector cellsusingthe ectonucleotidases. As a result, tumor growth in aged mice can be reversed by blockingthe function and/or recruitment of DP8 cells to tumors, while check-point inhibition with anti-PD1 Ab increases DP8 cells and drives tumor expansion.This tumor-enhancing mechanism of DP8 recruitment appears to be also active in older humans, aswe find DP8-like cells in various tumors, including late onset breast cancer.We propose that this novel tumor-promoting activity of CD8+T cells needs to be considered in the development of therapeutics tailored for the elderly. Overall design: Transcriptome analysis of CD45+ cells from Young AT3 (n=3), Old AT3 (n=3) Young B16 (n=3), and Old B16 (n=3) tumors