细胞毒性T细胞
CD8型
癌症研究
生物
免疫疗法
免疫学
免疫系统
细胞生物学
生物化学
体外
作者
Ryo Koyama‐Nasu,Motoko Kimura,Masahiro Kiuchi,Ami Aoki,Yangsong Wang,Yukiyoshi Mita,Ichita Hasegawa,Yutaka Endo,Atsushi Onodera,Kiyoshi Hirahara,Shinichiro Motohashi,Toshinori Nakayama
出处
期刊:Cancer immunology research
[American Association for Cancer Research]
日期:2023-05-22
卷期号:11 (8): 1085-1099
被引量:5
标识
DOI:10.1158/2326-6066.cir-22-0406
摘要
Tumor-specific CD8+ T cells play a pivotal role in antitumor immunity and are a key target of immunotherapeutic approaches. Intratumoral CD8+ T cells are heterogeneous; Tcf1+ stemlike CD8+ T cells give rise to their cytotoxic progeny-Tim-3+ terminally differentiated CD8+ T cells. However, where and how this differentiation process occurs has not been elucidated. We herein show that terminally differentiated CD8+ T cells can be generated within tumor-draining lymph nodes (TDLN) and that CD69 expression on tumor-specific CD8+ T cells controls its differentiation process through regulating the expression of the transcription factor TOX. In TDLNs, CD69 deficiency diminished TOX expression in tumor-specific CD8+ T cells, and consequently promoted generation of functional terminally differentiated CD8+ T cells. Anti-CD69 administration promoted the generation of terminally differentiated CD8+ T cells, and the combined use of anti-CD69 and anti-programmed cell death protein 1 (PD-1) showed an efficient antitumor effect. Thus, CD69 is an attractive target for cancer immunotherapy that synergizes with immune checkpoint blockade.
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