Co-expression of CD39 and CD103 identifies tumor-reactive CD8 T cells in human solid tumors

TLDR

Identifying tumor antigen‑specific T cells from cancer patients has important implications for immunotherapy diagnostics and therapeutics. We demonstrate that CD103⁺CD39⁺ tumor‑infiltrating CD8 T cells are enriched for tumor‑reactive, exhausted tissue‑resident memory cells across six malignancies, possess a distinct TCR repertoire with tumor‑expanded clones, efficiently kill autologous tumor cells in an MHC‑I–dependent manner, and higher frequencies correlate with improved overall survival in head and neck cancer, providing a strategy to identify tumor‑reactive T cells for immunotherapy development.

Abstract

Abstract 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.