Identifying tumor antigen-specific T cells from cancer patients has important implications for immunotherapy diagnostics and therapeutics. Here, we show that CD103+CD39+ tumor-infiltrating CD8 T cells (CD8 TIL) are enriched for tumor-reactive cells both in primary and metastatic tumors. This CD8 TIL subset is found across six different malignancies and displays an exhausted tissue-resident memory phenotype. CD103+CD39+ CD8 TILs have a distinct T-cell receptor (TCR) repertoire, with T-cell clones expanded in the tumor but present at low frequencies in the periphery. CD103+CD39+ CD8 TILs also efficiently kill autologous tumor cells in a MHC-class I-dependent manner. Finally, higher frequencies of CD103+CD39+ CD8 TILs in patients with head and neck cancer are associated with better overall survival. Our data thus describe an approach for detecting tumor-reactive CD8 TILs that will help define mechanisms of existing immunotherapy treatments, and may lead to future adoptive T-cell cancer therapies.
Duhen, Thomas; Duhen, Rebekka; Montler, Ryan; Moses, Jake; Moudgil, Tarsem; de Miranda, Noel F; Goodall, Cheri P; Blair, Tiffany C; Fox, Bernard A; McDermott, Jason E; Chang, Shu-Ching; Grunkemeier, Gary; Leidner, Rom; Bell, Richard Bryan; and Weinberg, Andrew D, "Co-expression of CD39 and CD103 identifies tumor-reactive CD8 T cells in human solid tumors." (2018). All Publications. 244.