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

Thomas Duhen (), Rebekka Duhen, Ryan Montler, Jake Moses, Tarsem Moudgil, Noel F. de Miranda, Cheri P. Goodall, Tiffany C. Blair, Bernard A. Fox, Jason E. McDermott, Shu-Ching Chang, Gary Grunkemeier, Rom Leidner, Richard Bryan Bell and Andrew D. Weinberg ()
Additional contact information
Thomas Duhen: AgonOx, Inc.
Rebekka Duhen: Earle A. Chiles Research Institute, Providence Cancer Institute
Ryan Montler: AgonOx, Inc.
Jake Moses: AgonOx, Inc.
Tarsem Moudgil: Earle A. Chiles Research Institute, Providence Cancer Institute
Noel F. de Miranda: Leiden University Medical Center
Cheri P. Goodall: Earle A. Chiles Research Institute, Providence Cancer Institute
Tiffany C. Blair: AgonOx, Inc.
Bernard A. Fox: Earle A. Chiles Research Institute, Providence Cancer Institute
Jason E. McDermott: Pacific Northwest National Laboratory, Computational Biology and Bioinformatics Group, MSIN: J4-33
Shu-Ching Chang: Providence Saint Joseph’s Health
Gary Grunkemeier: Providence Saint Joseph’s Health
Rom Leidner: Earle A. Chiles Research Institute, Providence Cancer Institute
Richard Bryan Bell: Earle A. Chiles Research Institute, Providence Cancer Institute
Andrew D. Weinberg: AgonOx, Inc.

Nature Communications, 2018, vol. 9, issue 1, 1-13

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.

Date: 2018
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DOI: 10.1038/s41467-018-05072-0

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