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Spatial dynamics of CD39+CD8+ exhausted T cell reveal tertiary lymphoid structures-mediated response to PD-1 blockade in esophageal cancer

Author

Listed:
  • Kenro Tanoue

    (Kyushu University)

  • Hirofumi Ohmura

    (Kyushu University
    Kyushu University)

  • Koki Uehara

    (Kyushu University)

  • Mamoru Ito

    (Kyushu University)

  • Kyoko Yamaguchi

    (Kyushu University)

  • Kenji Tsuchihashi

    (Kyushu University)

  • Yudai Shinohara

    (Japan Community Healthcare Organization Kyushu Hospital)

  • Peng Lu

    (Washington University in St. Louis)

  • Shingo Tamura

    (NHO National Hospital Organization Kyushu Medical Center)

  • Hozumi Shimokawa

    (Hamanomachi Hospital)

  • Taichi Isobe

    (Kyushu University
    Kyushu University)

  • Hiroshi Ariyama

    (Kitakyushu Municipal Medical Center)

  • Yoshihiro Shibata

    (Fukuoka Wajiro Hospital)

  • Risa Tanaka

    (St Mary’s Hospital)

  • Hitoshi Kusaba

    (Hamanomachi Hospital)

  • Taito Esaki

    (National Kyushu Cancer Center)

  • Kenji Mitsugi

    (Sasebo Kyosai Hospital)

  • Daisuke Kiyozawa

    (Kyushu University)

  • Takeshi Iwasaki

    (Kyushu University)

  • Hidetaka Yamamoto

    (Kyushu University
    Okayama University)

  • Yoshinao Oda

    (Kyushu University)

  • Koichi Akashi

    (Kyushu University)

  • Eishi Baba

    (Kyushu University)

Abstract

Despite the success of immune checkpoint blockade (ICB) therapy for esophageal squamous cell cancer, the key immune cell populations that affect ICB efficacy remain unclear. Here, imaging mass cytometry of tumor tissues from ICB-treated patients identifies a distinct cell population of CD39+PD-1+CD8+ T cells, specifically the TCF1+ subset, precursor exhausted T (CD39+ Tpex) cells, which positively correlate with ICB benefit. CD39+ Tpex cells are predominantly in the stroma, while differentiated CD39+ exhausted T cells are abundantly and proximally within the parenchyma. Notably, CD39+ Tpex cells are concentrated within and around tertiary lymphoid structure (TLS). Accordingly, tumors harboring TLSs have more of these cells in tumor areas than tumors lacking TLSs, suggesting Tpex cell recruitment from TLSs to tumors. In addition, circulating CD39+ Tpex cells are also increased in responders following ICB therapy. Our findings show that this unique subpopulation of CD39+PD-1+CD8+ T cells is crucial for ICB benefit, and suggest a key role in TLS-mediated immune responses against tumors.

Suggested Citation

  • Kenro Tanoue & Hirofumi Ohmura & Koki Uehara & Mamoru Ito & Kyoko Yamaguchi & Kenji Tsuchihashi & Yudai Shinohara & Peng Lu & Shingo Tamura & Hozumi Shimokawa & Taichi Isobe & Hiroshi Ariyama & Yoshih, 2024. "Spatial dynamics of CD39+CD8+ exhausted T cell reveal tertiary lymphoid structures-mediated response to PD-1 blockade in esophageal cancer," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53262-w
    DOI: 10.1038/s41467-024-53262-w
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