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

Kenro Tanoue, Hirofumi Ohmura, Koki Uehara, Mamoru Ito, Kyoko Yamaguchi, Kenji Tsuchihashi, Yudai Shinohara, Peng Lu, Shingo Tamura, Hozumi Shimokawa, Taichi Isobe, Hiroshi Ariyama, Yoshihiro Shibata, Risa Tanaka, Hitoshi Kusaba, Taito Esaki, Kenji Mitsugi, Daisuke Kiyozawa, Takeshi Iwasaki, Hidetaka Yamamoto, Yoshinao Oda, Koichi Akashi and Eishi Baba ()
Additional contact information
Kenro Tanoue: Kyushu University
Hirofumi Ohmura: 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
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
Yoshinao Oda: Kyushu University
Koichi Akashi: Kyushu University
Eishi Baba: Kyushu University

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-53262-w

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