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<p>While progenitor-exhausted T cells (Tpex) expressing TCF1 and PD-1 are crucial for the therapeutic effect of immune checkpoint inhibitors (ICIs) with therapeutic anti-PD-1 antibodies (aPD-1), the dynamics of ICI-bound Tpex are not fully understood. In this study, we investigate ICI-bound T cells in detail using combined sequencing analysis at the single-cell level. By analyzing samples from gastrointestinal cancer patients with or without ICI treatment, we find that Tpex are enriched in proximal lymph nodes (LNs) and proliferate at a high rate after ICI treatment. Importantly, aPD-1 high-bound Tpex in LNs share T-cell receptor clonotypes with intratumoral exhausted CD8<sup>+</sup> T cells (Tex), suggesting their migration to tumor sites after ICI treatment. This study thus provides new insights into how ICIs enhance anti-tumor immunity by acting on Tpex in LNs, deepening our understanding of the cellular mechanisms underlying ICI therapy.</p>

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PD-1 antibody-bound progenitor-exhausted CD8+ T cells in lymph nodes boost PD-1-blockade anti-tumor immunity in gastrointestinal cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月8日

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  • Yohei Nose,
  • Yoshiaki Yasumizu,
  • Takuro Saito,
  • Yamami Nakamura,
  • Koichi Jinushi,
  • Kaoru Fujikawa,
  • Kota Momose,
  • Kotaro Yamashita,
  • Koji Tanaka,
  • Kazuyoshi Yamamoto,
  • Tomoki Makino,
  • Tsuyoshi Takahashi,
  • Azumi Ueyama,
  • Yukinori Kurokawa,
  • Eiichi Sato,
  • Naganari Ohkura,
  • Shimon Sakaguchi,
  • Hisashi Wada,
  • Hidetoshi Eguchi,
  • Yuichiro Doki

摘要

While progenitor-exhausted T cells (Tpex) expressing TCF1 and PD-1 are crucial for the therapeutic effect of immune checkpoint inhibitors (ICIs) with therapeutic anti-PD-1 antibodies (aPD-1), the dynamics of ICI-bound Tpex are not fully understood. In this study, we investigate ICI-bound T cells in detail using combined sequencing analysis at the single-cell level. By analyzing samples from gastrointestinal cancer patients with or without ICI treatment, we find that Tpex are enriched in proximal lymph nodes (LNs) and proliferate at a high rate after ICI treatment. Importantly, aPD-1 high-bound Tpex in LNs share T-cell receptor clonotypes with intratumoral exhausted CD8+ T cells (Tex), suggesting their migration to tumor sites after ICI treatment. This study thus provides new insights into how ICIs enhance anti-tumor immunity by acting on Tpex in LNs, deepening our understanding of the cellular mechanisms underlying ICI therapy.