报告题目：
Lineage tracking reveals dynamic relationships of T cells in colorectal cancer
报 告 人：张雷博士 北京大学 北大-清华生命科学联合中心
报告时间：2018年11月30日 上午 10:00
报告地点：柏彦大厦906
邀 请 人：大数据精准医疗高精尖创新中心 张永彪
报告摘要：
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 microsatelliteinstable (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.
报告人简介：
张雷，北京大学，北大-清华生命科学联合中心博士后（导师：张泽民），主要从事单细胞技术在癌症中的研究，先后参与“基于单细胞技术的结直肠癌肿瘤浸润T淋巴细胞研究”，“基于单细胞技术的结直肠癌肿瘤浸润免疫细胞相互作用关系研究”，“循环微小RNA作为乳腺癌早期诊断及预后标志物研究”等课题，为科技部重大项目“基于组学特征谱的肺癌分子分型体系研究”的子课题负责人。先后发表SCI论文7篇，以第一作者在《Nature》发表了博士后期间主要工作。
