细胞毒性T细胞
生物
CD8型
抗原
肿瘤抗原
癌症研究
T细胞
CD40
抗原提呈细胞
免疫系统
免疫学
分子生物学
免疫疗法
生物化学
体外
作者
Jason M. Schenkel,Rebecca H. Herbst,David Canner,Amy Li,Michelle Hillman,Sean-Luc Shanahan,Grace Gibbons,Olivia Smith,Jonathan Y. Kim,Peter M.K. Westcott,William L. Hwang,William A. Freed-Pastor,George Eng,Michael S. Cuoco,Patricia Rogers,Jin K. Park,M. Burger,Orit Rozenblatt-Rosen,Le Cong,Kristen E. Pauken,Aviv Regev,Tyler Jacks
出处
期刊:Immunity
[Elsevier]
日期:2021-10-01
卷期号:54 (10): 2338-2353.e6
被引量:119
标识
DOI:10.1016/j.immuni.2021.08.026
摘要
In tumors, a subset of CD8+ T cells expressing the transcription factor TCF-1 drives the response to immune checkpoint blockade. We examined the mechanisms that maintain these cells in an autochthonous model of lung adenocarcinoma. Longitudinal sampling and single-cell sequencing of tumor-antigen specific TCF-1+ CD8+ T cells revealed that while intratumoral TCF-1+ CD8+ T cells acquired dysfunctional features and decreased in number as tumors progressed, TCF-1+ CD8+ T cell frequency in the tumor draining LN (dLN) remained stable. Two discrete intratumoral TCF-1+ CD8+ T cell subsets developed over time—a proliferative SlamF6+ subset and a non-cycling SlamF6− subset. Blocking dLN egress decreased the frequency of intratumoral SlamF6+ TCF-1+ CD8+ T cells. Conventional type I dendritic cell (cDC1) in dLN decreased in number with tumor progression, and Flt3L+anti-CD40 treatment recovered SlamF6+ T cell frequencies and decreased tumor burden. Thus, cDC1s in tumor dLN maintain a reservoir of TCF-1+ CD8+ T cells and their decrease contributes to failed anti-tumor immunity.
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