PNNL

Abstract

Identifying tumor antigen-specific T cells from cancer patients has been a goal of tumor immunologists for several decades. Here we show that co-expression of CD103 and CD39 on CD8 TIL highly enriched for tumor-reactive T cells. This cell population, which is only present in TIL from primary and metastatic tumors, exhibited features of exhausted cells and displayed characteristics of tissue-resident memory T cells. CD39+CD103+ CD8 TIL had a distinct TCR repertoire compared to other CD8 TIL subsets and were clonally expanded within the tumor. They were highly enriched for tumor antigen recognition and efficiently killed autologous tumor cells. Finally, patients with head and neck cancer whose CD8 TIL contained a higher frequency of CD39+CD103+ cells experienced a greater overall survival. This work describes a simple method for detecting tumor-reactive CD8 TIL, which should help define mechanisms of current immunotherapies and may lead to the development of future immunotherapies.