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

Nature Communications
Thomas DuhenAndrew D Weinberg

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.

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Datasets Mentioned

BETA
GSE114944

Methods Mentioned

BETA
flow cytometry
FACS
chip
enzyme-linked immunosorbent assay

Software Mentioned

R
survMisc
RTCGA
R package ‘ survminer
GraphPad Prism
Affymetrix GeneChip Command Console ( AGCC )
ImmunoSEQ Analyzer
Volcano
maxstat R package
ggplot2 R

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