Extended Data Fig. 9: DP8-like cells are present in humans.

Representative gating strategy of exhaustion markers expressed on DP and SP38 human CD8+ cells (a) and frequency of exhausted-like SP39 in CD8+ T cells from human PBMCs activated for 12 days with anti-CD3/28 Ab-beads (b). (c) Normalized enrichment score (NES) of GSEA for top 300 genes from human breast cancer TIL CD8+ T cells (GSE110686) in A-AT3 DP8 versus Y-AT3 DP8 and A-AT3 DP8 versus A-B16 DP8. (d) Summary abstract showing that healthy aging increases CXCR6+ DP8 cells via B cells presenting cognate antigens, which presumably occurs in LNs. Upon recruitment into the tumor tissue expressing CXCL16, CXCR6+ DP8 cells upregulate exhausted-like phenotype and importantly, promote tumor growth via inhibiting antitumor effector cells at least in part by hydrolyzing eATP and possibly generating immunosuppressive molecules. Shown is frequency ± SEM (b), where each symbol is for a single donor, n = 6-8 people per group. Experiments were reproduced three times. ** P < 0.01; *** P < 0.001 in unpaired Mann-Whitney test.