CD8型
免疫疗法
生物
癌症研究
T细胞
免疫系统
免疫学
作者
Cem Sievers,Marco Craveiro,Jay Friedman,Yvette Robbins,Xinping Yang,Ke Bai,Andrew Nguyen,Jason Redman,Raj Chari,Patrick Soon‐Shiong,Jeffrey Schlom,James L. Gulley,Clint Allen
出处
期刊:Cancer Cell
[Elsevier]
日期:2023-05-01
卷期号:41 (5): 887-902.e5
被引量:13
标识
DOI:10.1016/j.ccell.2023.03.014
摘要
Neoadjuvant immunotherapies (NITs) have led to clinical benefits in several cancers. Characterization of the molecular mechanisms underlying responses to NIT may lead to improved treatment strategies. Here we show that exhausted, tumor-infiltrating CD8+ T (Tex) cells display local and systemic responses to concurrent neoadjuvant TGF-β and PD-L1 blockade. NIT induces a significant and selective increase in circulating Tex cells associated with reduced intratumoral expression of the tissue-retention marker CD103. TGF-β-driven CD103 expression on CD8+ T cells is reversed following TGF-β neutralization in vitro, implicating TGF-β in T cell tissue retention and impaired systemic immunity. Transcriptional changes implicate T cell receptor signaling and glutamine metabolism as important determinants of enhanced or reduced Tex treatment response, respectively. Our analysis illustrates physiological and metabolic changes underlying T cell responses to NIT, highlighting the interplay between immunosuppression, tissue retention, and systemic anti-tumor immunity and suggest antagonism of T cell tissue retention as a promising neoadjuvant treatment strategy.
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