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.
Highlights
Identifying tumor antigen-specific tumor cells in medium without exogenous IL-15 (T cell) from cancer patients has important implications for immunotherapy diagnostics and therapeutics
Recent work has shown that tumor-reactive CD8 T cells can be found within the CD103+ subset of TILs from patients with high-grade serous ovarian cancer (HGSC) and non-small cell lung cancer (NSCLC)[12,15]
To further explore the CD103+ CD8 TIL subset, we examined the expression of CD39, PD-1, CD127, and additional cell surface markers associated with activation/exhaustion in a patient with head and neck squamous cell carcinoma (HNSCC)
Summary
Identifying tumor antigen-specific T cells from cancer patients has important implications for immunotherapy diagnostics and therapeutics. We show that co-expression of CD39 and CD103 identifies a unique population of CD8 TILs found only within the tumor microenvironment These cells, which have a TRM phenotype and express high levels of exhaustion markers, have a high frequency of tumor-reactive cells, have a distinct TCR repertoire and are capable of recognizing and killing autologous tumor cells. There is a greater overall survival (OS) in head and neck cancer patients that have a higher frequency of CD103 +CD39+ CD8 TILs at time of surgery These data provide an approach to identify tumor-reactive CD8 T cells and will have important ramifications for developing future therapeutic strategies
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