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
Abstract 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.