Defining T Cell States Associated with Response to Checkpoint Immunotherapy in Melanoma.
Defining T Cell States Associated with Response to Checkpoint Immunotherapy in Melanoma.
复制标题
DOI：
10.1016/j.cell.2018.10.038
复制
发表时间：
2018-11-01
期刊：
影响因子：
64.5
通讯作者：
Hacohen N
中科院分区：
文献类型：
--
作者：
Sade-Feldman M;Yizhak K;Bjorgaard SL;Ray JP;de Boer CG;Jenkins RW;Lieb DJ;Chen JH;Frederick DT;Barzily-Rokni M;Freeman SS;Reuben A;Hoover PJ;Villani AC;Ivanova E;Portell A;Lizotte PH;Aref AR;Eliane JP;Hammond MR;Vitzthum H;Blackmon SM;Li B;Gopalakrishnan V;Reddy SM;Cooper ZA;Paweletz CP;Barbie DA;Stemmer-Rachamimov A;Flaherty KT;Wargo JA;Boland GM;Sullivan RJ;Getz G;Hacohen N
免疫检查点阻断疗法已经彻底改变了癌症的治疗。尽管对晚期黑色素瘤的反应率很高，但大多数患者还是死于疾病。为了确定与检查点治疗成功或失败相关的因素，我们分析了48例接受检查点抑制剂治疗的黑色素瘤患者肿瘤样本中的16,291个个体免疫细胞的转录组。CD8+ T细胞的两种不同状态通过聚类来定义，并与患者肿瘤的消退或进展相关。单个转录因子TCF7在固定肿瘤样本的CD8+ T细胞中可见，并在检查点治疗患者的独立队列中预测阳性临床结果。我们描述了这些T细胞状态的表观遗传景观和克隆性，并通过针对衰竭细胞中因子的新组合证明了增强的抗肿瘤免疫。我们对肿瘤免疫细胞转录组的研究证明了一种识别预测因子、机制和靶点的策略，可以增强检查点免疫治疗。对黑色素瘤免疫细胞的单细胞分析揭示了细胞毒性T细胞群中的TCF7+记忆样状态，并证明其与阳性结果相关
Treatment of cancer has been revolutionized by immune checkpoint blockade therapies. Despite the high rate of response in advanced melanoma, the majority of patients succumb to disease. To identify factors associated with success or failure of checkpoint therapy, we profiled transcriptomes of 16,291 individual immune cells from 48 tumor samples of melanoma patients treated with checkpoint inhibitors. Two distinct states of CD8+ T cells were defined by clustering, and associated with patient tumor regression or progression. A single transcription factor, TCF7, was visualized within CD8+ T cells in fixed tumor samples and predicted positive clinical outcome in an independent cohort of checkpoint-treated patients. We delineated the epigenetic landscape and clonality of these T cell states, and demonstrated enhanced anti-tumor immunity by targeting novel combinations of factors in exhausted cells. Our study of immune cell transcriptomes from tumors demonstrates a strategy for identifying predictors, mechanisms and targets for enhancing checkpoint immunotherapy. Single cell analysis of immune cells from melanoma uncovers a TCF7+ memory-like state in the cytotoxic T cell population, and demonstrates its association with a positive outcome
登录
查看更多内容
影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
28.2
作者：
Chen PL;Roh W;Reuben A;Cooper ZA;Spencer CN;Prieto PA;Miller JP;Bassett RL;Gopalakrishnan V;Wani K;De Macedo MP;Austin-Breneman JL;Jiang H;Chang Q;Reddy SM;Chen WS;Tetzlaff MT;Broaddus RJ;Davies MA;Gershenwald JE;Haydu L;Lazar AJ;Patel SP;Hwu P;Hwu WJ;Diab A;Glitza IC;Woodman SE;Vence LM;Wistuba II;Amaria RN;Kwong LN;Prieto V;Davis RE;Ma W;Overwijk WW;Sharpe AH;Hu J;Futreal PA;Blando J;Sharma P;Allison JP;Chin L;Wargo JA
通讯作者：
Wargo JA
影响因子：
64.8
作者：
Im SJ;Hashimoto M;Gerner MY;Lee J;Kissick HT;Burger MC;Shan Q;Hale JS;Lee J;Nasti TH;Sharpe AH;Freeman GJ;Germain RN;Nakaya HI;Xue HH;Ahmed R
通讯作者：
Ahmed R
影响因子：
12.3
作者：
Carpenter AE;Jones TR;Lamprecht MR;Clarke C;Kang IH;Friman O;Guertin DA;Chang JH;Lindquist RA;Moffat J;Golland P;Sabatini DM
通讯作者：
Sabatini DM