肿瘤微环境
旁观者效应
细胞因子
生物
免疫系统
细胞生物学
癌症研究
免疫突触
免疫学
T细胞
T细胞受体
作者
Ronan Thibaut,Pierre Bost,Idan Milo,Marine Cazaux,Fabrice Lemaı̂tre,Zacarias Garcia,Ido Amit,Béatrice Breart,Clémence Cornuot,Benno Schwikowski,Philippe Bousso
出处
期刊:Nature cancer
[Springer Nature]
日期:2020-03-09
卷期号:1 (3): 302-314
被引量:93
标识
DOI:10.1038/s43018-020-0038-2
摘要
The cytokine IFN-γ produced by tumor-reactive T cells is a key effector molecule with pleiotropic effects during anti-tumor immune responses. While IFN-γ production is targeted at the immunological synapse, its spatiotemporal activity within the tumor remains elusive. Here, we report that while IFN-γ secretion requires local antigen recognition, IFN-γ diffuses extensively to alter the tumor microenvironment in distant areas. Using intravital imaging and a reporter for STAT1 translocation, we provide evidence that T cells mediate sustained IFN-γ signaling in remote tumor cells. Furthermore, tumor phenotypic alterations required several hours of exposure to IFN-γ, a feature that disfavored local IFN-γ activity over diffusion and bystander activity. Finally, single-cell RNA-seq data from melanoma patients also suggested bystander IFN-γ activity in human tumors. Thus, tumor-reactive T cells act collectively to create large cytokine fields that profoundly modify the tumor microenvironment.
科研通智能强力驱动
Strongly Powered by AbleSci AI