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

Author

Listed:
  • 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.
    Earle A. Chiles Research Institute, Providence Cancer Institute)

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.

Suggested Citation

  • 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 Grun, 2018. "Co-expression of CD39 and CD103 identifies tumor-reactive CD8 T cells in human solid tumors," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05072-0
    DOI: 10.1038/s41467-018-05072-0
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    1. Rui Sun & Chao Lei & Zhishan Xu & Xuemei Gu & Liu Huang & Liang Chen & Yi Tan & Min Peng & Kavitha Yaddanapudi & Leah Siskind & Maiying Kong & Robert Mitchell & Jun Yan & Zhongbin Deng, 2024. "Neutral ceramidase regulates breast cancer progression by metabolic programming of TREM2-associated macrophages," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    2. Nasser K. Altorki & Zachary H. Walsh & Johannes C. Melms & Jeffery L. Port & Benjamin E. Lee & Abu Nasar & Cathy Spinelli & Lindsay Caprio & Meri Rogava & Patricia Ho & Paul J. Christos & Ashish Saxen, 2023. "Neoadjuvant durvalumab plus radiation versus durvalumab alone in stages I–III non-small cell lung cancer: survival outcomes and molecular correlates of a randomized phase II trial," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    3. Jia-Cheng Lu & Lei-Lei Wu & Yi-Ning Sun & Xiao-Yong Huang & Chao Gao & Xiao-Jun Guo & Hai-Ying Zeng & Xu-Dong Qu & Yi Chen & Dong Wu & Yan-Zi Pei & Xian-Long Meng & Yi-Min Zheng & Chen Liang & Peng-Fe, 2024. "Macro CD5L+ deteriorates CD8+T cells exhaustion and impairs combination of Gemcitabine-Oxaliplatin-Lenvatinib-anti-PD1 therapy in intrahepatic cholangiocarcinoma," Nature Communications, Nature, vol. 15(1), pages 1-23, December.

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