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人类膀胱癌的瘤内CD4+T细胞介导抗肿瘤细胞毒性作用
2020-06-05 10:07

美国加州大学圣迭戈分校Lawrence Fong、Chun Jimmie Ye等研究人员合作发现,人类膀胱癌的瘤内CD4+T细胞介导抗肿瘤细胞毒性作用。相关论文于2020年6月3日在线发表在《细胞》杂志上。

通过使用单细胞RNA和配对T细胞受体(TCR)测序对来自7位患者的30604个T细胞进行检测,研究人员评估了来自人膀胱肿瘤和非恶性组织的T细胞。研究人员发现,与非恶性组织相比,CD8+T细胞的状态和组成在肿瘤中并不明显。相反,CD4+T细胞的单细胞分析显示了几种肿瘤特异性状态,包括调节性T细胞的多个不同状态。
 
令人惊讶地,研究人员还发现了克隆扩增的多种细胞毒性CD4+T细胞状态。这些CD4+T细胞能够以MHC II依赖性方式杀死自体肿瘤,并被调节性T细胞抑制。此外,肿瘤中细胞毒性CD4+T细胞的基因特征能够预测244位接受抗PD-L1治疗的转移性膀胱癌患者的临床反应。
 
据了解,抗PD-1免疫疗法很少在膀胱癌中产生效果。介导肿瘤排斥的特异性T细胞尚不清楚。
 
附:英文原文

Title: Intratumoral CD4+ T Cells Mediate Anti-tumor Cytotoxicity in Human Bladder Cancer

Author: David Y. Oh, Serena S. Kwek, Siddharth S. Raju, Tony Li, Elizabeth McCarthy, Eric Chow, Dvir Aran, Arielle Ilano, Chien-Chun Steven Pai, Chiara Rancan, Kathryn Allaire, Arun Burra, Yang Sun, Matthew H. Spitzer, Serghei Mangul, Sima Porten, Maxwell V. Meng, Terence W. Friedlander, Chun Jimmie Ye, Lawrence Fong

Issue&Volume: 2020-06-03

Abstract: Responses to anti-PD-1 immunotherapy occur but are infrequent in bladder cancer. The specific T cells that mediate tumor rejection are unknown. T cells from human bladder tumors and non-malignant tissue were assessed with single-cell RNA and paired T cell receptor (TCR) sequencing of 30,604 T cells from 7 patients. We find that the states and repertoires of CD8+ T cells are not distinct in tumors compared with non-malignant tissues. In contrast, single-cell analysis of CD4+ T cells demonstrates several tumor-specific states, including multiple distinct states of regulatory T cells. Surprisingly, we also find multiple cytotoxic CD4+ T cell states that are clonally expanded. These CD4+ T cells can kill autologous tumors in an MHC class II-dependent fashion and are suppressed by regulatory T cells. Further, a gene signature of cytotoxic CD4+ T cells in tumors predicts a clinical response in 244 metastatic bladder cancer patients treated with anti-PD-L1.

DOI: 10.1016/j.cell.2020.05.017

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30612-7

Cell:《细胞》,创刊于1974年。隶属于细胞出版社,最新IF:66.85
官方网址:https://www.cell.com/
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本期文章:《细胞》:Online/在线发表

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