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

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. Furthermore, 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.
Authors:
 [1] ;  [2] ;  [1] ;  [1] ;  [2] ;  [3] ;  [2] ;  [1] ;  [2] ; ORCiD logo [4] ;  [5] ;  [5] ;  [2] ;  [2] ;  [6]
  1. AgonOx, Inc., Portland, OR (United States)
  2. Providence Cancer Institute, Portland, OR (United States)
  3. Leiden Univ. Medical Center, Leiden (The Netherlands)
  4. Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
  5. Providence Saint Joseph's Health, Portland, OR (United States)
  6. AgonOx, Inc., Portland, OR (United States); Providence Cancer Institute, Portland, OR (United States)
Publication Date:
Report Number(s):
PNNL-SA135245
Journal ID: ISSN 2041-1723; PII: 5072
Grant/Contract Number:
AC05-76RL01830
Type:
Accepted Manuscript
Journal Name:
Nature Communications
Additional Journal Information:
Journal Volume: 9; Journal Issue: 1; Journal ID: ISSN 2041-1723
Publisher:
Nature Publishing Group
Research Org:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org:
USDOE
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES
OSTI Identifier:
1463347

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., 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.. 2018. "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. https://www.osti.gov/servlets/purl/1463347.
@article{osti_1463347,
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 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. Furthermore, 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.},
doi = {10.1038/S41467-018-05072-0},
journal = {Nature Communications},
number = 1,
volume = 9,
place = {United States},
year = {2018},
month = {7}
}

Works referenced in this record:

Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles
journal, September 2005
  • Subramanian, A.; Tamayo, P.; Mootha, V. K.
  • Proceedings of the National Academy of Sciences, Vol. 102, Issue 43, p. 15545-15550
  • DOI: 10.1073/pnas.0506580102

Adoptive T cell therapy using antigen-specific CD8+ T cell clones for the treatment of patients with metastatic melanoma: In vivo persistence, migration, and antitumor effect of transferred T cells
journal, November 2002
  • Yee, C.; Thompson, J. A.; Byrd, D.
  • Proceedings of the National Academy of Sciences, Vol. 99, Issue 25, p. 16168-16173
  • DOI: 10.1073/pnas.242600099