CTL公司*
免疫疗法
免疫检查点
细胞毒性T细胞
渗透(HVAC)
免疫系统
癌症研究
医学
黑色素瘤
封锁
癌症免疫疗法
PD-L1
T细胞
肿瘤科
免疫学
内科学
生物
CD8型
受体
体外
物理
热力学
生物化学
作者
Peng Jiang,Shengqing Gu,Deng Pan,Jingxin Fu,Avinash Sahu,Xihao Hu,Ziyi Li,Nicole Traugh,Xia Bu,Bo Li,Jun Li,Gordon J. Freeman,Myles Brown,Kai W. Wucherpfennig,X. Shirley Liu
出处
期刊:Nature Medicine
[Springer Nature]
日期:2018-08-20
卷期号:24 (10): 1550-1558
被引量:2796
标识
DOI:10.1038/s41591-018-0136-1
摘要
Cancer treatment by immune checkpoint blockade (ICB) can bring long-lasting clinical benefits, but only a fraction of patients respond to treatment. To predict ICB response, we developed TIDE, a computational method to model two primary mechanisms of tumor immune evasion: the induction of T cell dysfunction in tumors with high infiltration of cytotoxic T lymphocytes (CTL) and the prevention of T cell infiltration in tumors with low CTL level. We identified signatures of T cell dysfunction from large tumor cohorts by testing how the expression of each gene in tumors interacts with the CTL infiltration level to influence patient survival. We also modeled factors that exclude T cell infiltration into tumors using expression signatures from immunosuppressive cells. Using this framework and pre-treatment RNA-Seq or NanoString tumor expression profiles, TIDE predicted the outcome of melanoma patients treated with first-line anti-PD1 or anti-CTLA4 more accurately than other biomarkers such as PD-L1 level and mutation load. TIDE also revealed new candidate ICB resistance regulators, such as SERPINB9, demonstrating utility for immunotherapy research.
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