CD8型
癌症研究
细胞毒性T细胞
免疫疗法
免疫检查点
医学
祖细胞
封锁
T细胞
细胞
免疫系统
生物
免疫学
内科学
干细胞
细胞生物学
受体
体外
生物化学
遗传学
作者
Zhi-Chao Liu,Yaru Zhang,Ning Ma,Yang� Yang,Yunlong Ma,Rui Wang,Yan Wang,Jinzhi Wei,Hongyan Chen,Alfredo Tartarone,Jeffrey B. Velotta,Farshid Dayyani,Emmanuel Gabriel,Connor Wakefield,Biniam Kidane,Cristiano Carbonelli,Ling Long,Zhihua Liu,Jianzhong Su,Zhigang Li
出处
期刊:Cancer Cell
[Elsevier]
日期:2023-11-01
卷期号:41 (11): 1852-1870.e9
被引量:7
标识
DOI:10.1016/j.ccell.2023.09.011
摘要
Neoadjuvant immune checkpoint blockade (ICB) demonstrates promise in operable esophageal squamous cell carcinoma (ESCC), but lacks available efficacy biomarkers. Here, we perform single-cell RNA-sequencing of tumors from patients with ESCC undergoing neoadjuvant ICB, revealing a subset of exhausted CD8+ T cells expressing SPRY1 (CD8+ Tex-SPRY1) that displays a progenitor exhausted T cell (Tpex) phenotype and correlates with complete response to ICB. We validate CD8+ Tex-SPRY1 cells as an ICB-specific predictor of improved response and survival using independent ICB-/non-ICB cohorts and demonstrate that expression of SPRY1 in CD8+ T cells enforces Tpex phenotype and enhances ICB efficacy. Additionally, CD8+ Tex-SPRY1 cells contribute to proinflammatory phenotype of macrophages and functional state of B cells, which thereby promotes antitumor immunity by enhancing CD8+ T cell effector functions. Overall, our findings unravel progenitor-like CD8+ Tex-SPRY1 cells’ role in effective responses to ICB for ESCC and inform mechanistic biomarkers for future individualized immunotherapy.
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