肺癌
CD8型
腺癌
生物
细胞毒性T细胞
T细胞
癌症研究
单细胞测序
癌症
肺
抗原
细胞
免疫学
医学
免疫系统
基因
病理
内科学
表型
外显子组测序
遗传学
体外
作者
Xinyi Guo,Yuanyuan Zhang,Liangtao Zheng,Chunhong Zheng,Jintao Song,Qiming Zhang,Boxi Kang,Zhouzerui Liu,Liang Jin,Rui Xing,Ranran Gao,Lei Zhang,Minghua Dong,Xueda Hu,Xianwen Ren,Dennis Kirchhoff,Helge G. Roider,Tiansheng Yan,Zemin Zhang
出处
期刊:Nature Medicine
[Springer Nature]
日期:2018-06-25
卷期号:24 (7): 978-985
被引量:1204
标识
DOI:10.1038/s41591-018-0045-3
摘要
Cancer immunotherapies have shown sustained clinical responses in treating non-small-cell lung cancer1-3, but efficacy varies and depends in part on the amount and properties of tumor infiltrating lymphocytes4-6. To depict the baseline landscape of the composition, lineage and functional states of tumor infiltrating lymphocytes, here we performed deep single-cell RNA sequencing for 12,346 T cells from 14 treatment-naïve non-small-cell lung cancer patients. Combined expression and T cell antigen receptor based lineage tracking revealed a significant proportion of inter-tissue effector T cells with a highly migratory nature. As well as tumor-infiltrating CD8+ T cells undergoing exhaustion, we observed two clusters of cells exhibiting states preceding exhaustion, and a high ratio of "pre-exhausted" to exhausted T cells was associated with better prognosis of lung adenocarcinoma. Additionally, we observed further heterogeneity within the tumor regulatory T cells (Tregs), characterized by the bimodal distribution of TNFRSF9, an activation marker for antigen-specific Tregs. The gene signature of those activated tumor Tregs, which included IL1R2, correlated with poor prognosis in lung adenocarcinoma. Our study provides a new approach for patient stratification and will help further understand the functional states and dynamics of T cells in lung cancer.
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