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Nat Commun. 2018 Jul 13;9(1):2724. doi: 10.1038/s41467-018-05072-0.

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

Author information

1
AgonOx, Inc., 4805 NE Glisan Street 2N35, Portland, OR, 97213, USA. thomas.duhen@agonox.com.
2
Earle A. Chiles Research Institute, Providence Cancer Institute, 4805 NE Glisan Street 2N35, Portland, OR, 97213, USA.
3
AgonOx, Inc., 4805 NE Glisan Street 2N35, Portland, OR, 97213, USA.
4
Department of Pathology, Leiden University Medical Center, P1-43, LUMC, Albinusdreef 2, 2333, Leiden, The Netherlands.
5
Pacific Northwest National Laboratory, Computational Biology and Bioinformatics Group, MSIN: J4-33, 902 Battelle Boulevard, PO Box 999, Richland, WA, 99352, USA.
6
Medical Data Research Center, Providence Saint Joseph's Health, 9205 SW Barnes Road, Portland, OR, 97225, USA.
7
AgonOx, Inc., 4805 NE Glisan Street 2N35, Portland, OR, 97213, USA. andrew.weinberg@providence.org.
8
Earle A. Chiles Research Institute, Providence Cancer Institute, 4805 NE Glisan Street 2N35, Portland, OR, 97213, USA. andrew.weinberg@providence.org.

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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