Lineage tracking reveals dynamic relationships of T cells in colorectal cancer

T cells are key elements of cancer immunotherapy, but certain fundamental properties, such as development and migration of T cells within tumours, remain elusive. The enormous T cell receptor (TCR) repertoire, which is required for recognising foreign and self-antigens, could serve as lineage tags to track these T cells in tumours. Here, we obtained transcriptomes of 11,138 single T cells from 12 patients with colorectal cancer (CRC) and developed STARTRAC (single T-cell analysis by RNA-seq and TCR tracking) indices to quantitatively analyse dynamic relationships among 20 identified T cell subsets with distinct functions and clonalities. While both CD8+ effector and “exhausted” T cells exhibited high clonal expansion, they were independently connected with tumour-resident CD8+ effector memory cells, implicating a TCR-based fate decision. Of the CD4+ T cells, the majority of tumour-infiltrating Tregs showed clonal exclusivity, whereas certain Treg clones were developmentally linked to multiple TH clones. Notably, we identified two IFNG+ TH1-like clusters in tumours, the GZMK+ TEM and CXCL13+BHLHE40+ TH1-like clusters, which were associated with distinct IFN-γ-regulating transcription factors, EOMES/RUNX3 and BHLHE40, respectively. Only CXCL13+BHLHE40+ TH1-like cells were preferentially enriched in tumours of microsatellite-instable (MSI) patients, which might explain their favourable responses to immune-checkpoint blockade. Furthermore, IGFLR1 was highly expressed in both CXCL13+BHLHE40+ TH1-like and CD8+ exhausted T cells and possessed co-stimulatory functions. Our integrated STARTRAC analyses provide a powerful avenue to comprehensively dissect the T cell properties in CRC, which could provide new insights into the dynamic relationships of T cells in other cancers.

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《生物技术创新与创业》课程介绍

授课教师 张泽民 开课学期 秋季
课程名称 生物技术创新与创业 学  分 1
英文名称 Biotechnology Innovation and Entrepreneurship 授课对象(博/硕) 博士生、硕士生

课程简介:

近几年,随着新技术的发展和精准医疗概念的提出,生命科学领域的涌现大量科研成果和发现。但对于大多数研究来说,将新技术和新成果转化为面向大众的产品或服务模式使其发挥应有的价值仍然不甚明了。

本课程旨在通过生命科学业界精英结合个人发展和创业经历,以课程讲座等形式和学生分享包括产业发展历史,生物技术现状,生命科学发展前景,科研成果转化思路和创业创新思维等,使学生了解目前我国生命科学产业最前沿动态,丰富学生视野、提升学术能力,学习创新创业理念和技术成果转化经验,启发多向思考。

上课安排:

1-16周每单周上课 时间 地点 备注
9月19日 3:00-5:00 pm 二教423
10月3日
10月17日 3:00-5:00 pm 二教423 刘毓文
10月31日 3:00-5:00 pm 二教423 Jasmine Cui
11月14日 3:00-5:00 pm 二教423 刘立宇
11月28日 3:00-5:00 pm 二教423 李英睿,碳云
12月12日 3:00-5:00 pm 二教423 李瑞强
12月26日 3:00-5:00 pm 二教423

嘉宾介绍:

张泽民教授:http://cancer-pku.cn/index.php/people/zemin-zhang/

刘毓文:http://cancer-pku.cn/index.php/2018/10/08/yuwen-liu/

崔霁松:http://cancer-pku.cn/index.php/2018/10/27/jiabinjieshaocuijisong/

刘立宇:http://cancer-pku.cn/index.php/2018/11/05/jiabinjieshaoliuliyu/