2025-10-21 東京理科大学
<関連情報>
- https://www.tus.ac.jp/today/archive/20251016_1923.html
- https://www.nature.com/articles/s41467-025-64107-5
腫瘍内CD8+ T細胞の増殖を予測する汎免疫療法シグネチャー A pan-immunotherapy signature to predict intratumoral CD8+ T cell expansions
Munetomo Takahashi,Mikiya Tsunoda,Hiroyasu Aoki,Masaki Kurosu,Haru Ogiwara,Shigeyuki Shichino,David Bending,Shumpei Ishikawa,James E. D. Thaventhiran,Kouji Matsushima & Satoshi Ueha
Nature Communications Published:20 October 2025
DOI:https://doi.org/10.1038/s41467-025-64107-5
Abstract
Effective cancer immunotherapy relies on the clonal proliferation and expansion of CD8+ T cells in the tumor. However, our insights into clonal expansions are limited, owing to an inability to track the same clones in tumors over time. Here, we develop a multi-site tumor mouse model system to track hundreds of expanding and contracting CD8+ T cell clones over multiple timepoints in tumors of the same individual. Through coupling of clonal expansion dynamics and single-cell RNA/TCR-seq data, we identify a transcriptomic signature in PD-1+Ly108+ precursor exhausted cells that strongly predicts rates of intratumoral clone expansion. The signature correlates with expansion in mice, both with and without immunotherapies, and in patients undergoing PD-1 blockade therapy. Expression of the signature during treatment corresponds with positive clinical outcomes. Downregulation of the signature precedes clone contraction—a phase in which clones contract but maintain revivable precursor exhausted cells in the tumor. LAG-3 blockade re-activates the expansion signature, re-expanding pre-existing clones, including previously contracted clones. These findings reveal how the study of clonal expansion dynamics provide a powerful ‘pan-immunotherapy’ signature for monitoring immunotherapies with implications for their future development.
