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

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.

Authors:
; ; ; ; ; ; ; ; ; ORCiD logo; ; ; ; ;
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1503529
Report Number(s):
PNNL-SA-135245
Journal ID: ISSN 2041-1723
DOE Contract Number:  
AC05-76RL01830
Resource Type:
Journal Article
Journal Name:
Nature Communications
Additional Journal Information:
Journal Volume: 9; Journal Issue: 1; Journal ID: ISSN 2041-1723
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
cancer, immunotherapy, transcriptomics, t-cells, human

Citation Formats

Duhen, Thomas, Duhen, Rebekka, Montler, Ryan, Moses, Jake, Moudgil, Tarsem, de Miranda, Noel F., Goodall, Cheri P., Blair, Tiffany C., Fox, Bernard A., McDermott, Jason E., Chang, Shu-Ching, Grunkemeier, Gary, Leidner, Rom, Bell, Richard Bryan, and Weinberg, Andrew D. Co-expression of CD39 and CD103 identifies tumor-reactive CD8 T cells in human solid tumors. United States: N. p., 2018. Web. doi:10.1038/s41467-018-05072-0.
Duhen, Thomas, Duhen, Rebekka, Montler, Ryan, Moses, Jake, Moudgil, Tarsem, de Miranda, Noel F., Goodall, Cheri P., Blair, Tiffany C., Fox, Bernard A., McDermott, Jason E., Chang, Shu-Ching, Grunkemeier, Gary, Leidner, Rom, Bell, Richard Bryan, & Weinberg, Andrew D. Co-expression of CD39 and CD103 identifies tumor-reactive CD8 T cells in human solid tumors. United States. doi:10.1038/s41467-018-05072-0.
Duhen, Thomas, Duhen, Rebekka, Montler, Ryan, Moses, Jake, Moudgil, Tarsem, de Miranda, Noel F., Goodall, Cheri P., Blair, Tiffany C., Fox, Bernard A., McDermott, Jason E., Chang, Shu-Ching, Grunkemeier, Gary, Leidner, Rom, Bell, Richard Bryan, and Weinberg, Andrew D. Fri . "Co-expression of CD39 and CD103 identifies tumor-reactive CD8 T cells in human solid tumors". United States. doi:10.1038/s41467-018-05072-0.
@article{osti_1503529,
title = {Co-expression of CD39 and CD103 identifies tumor-reactive CD8 T cells in human solid tumors},
author = {Duhen, Thomas and Duhen, Rebekka and Montler, Ryan and Moses, Jake and Moudgil, Tarsem and de Miranda, Noel F. and Goodall, Cheri P. and Blair, Tiffany C. and Fox, Bernard A. and McDermott, Jason E. and Chang, Shu-Ching and Grunkemeier, Gary and Leidner, Rom and Bell, Richard Bryan and Weinberg, Andrew D.},
abstractNote = {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.},
doi = {10.1038/s41467-018-05072-0},
journal = {Nature Communications},
issn = {2041-1723},
number = 1,
volume = 9,
place = {United States},
year = {2018},
month = {7}
}

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