Author
Listed:
- Lei Zhang
(Peking University)
- Xin Yu
(Discovery Research, Amgen)
- Liangtao Zheng
(Peking University)
- Yuanyuan Zhang
(Peking University)
- Yansen Li
(Peking University People’s Hospital)
- Qiao Fang
(Peking University)
- Ranran Gao
(Peking University)
- Boxi Kang
(Peking University)
- Qiming Zhang
(Peking University)
- Julie Y. Huang
(Discovery Research, Amgen)
- Hiroyasu Konno
(Discovery Research, Amgen)
- Xinyi Guo
(Peking University)
- Yingjiang Ye
(Peking University People’s Hospital)
- Songyuan Gao
(Peking University People’s Hospital)
- Shan Wang
(Peking University People’s Hospital)
- Xueda Hu
(Peking University)
- Xianwen Ren
(Peking University)
- Zhanlong Shen
(Peking University People’s Hospital)
- Wenjun Ouyang
(Discovery Research, Amgen)
- Zemin Zhang
(Peking University
Peking University)
Abstract
T cells are key elements of cancer immunotherapy1 but certain fundamental properties, such as the development and migration of T cells within tumours, remain unknown. The enormous T cell receptor (TCR) repertoire, which is required for the recognition of foreign and self-antigens2, could serve as lineage tags to track these T cells in tumours3. Here we obtained transcriptomes of 11,138 single T cells from 12 patients with colorectal cancer, and developed single T cell analysis by RNA sequencing and TCR tracking (STARTRAC) indices to quantitatively analyse the dynamic relationships among 20 identified T cell subsets with distinct functions and clonalities. Although 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, most tumour-infiltrating T regulatory (Treg) cells showed clonal exclusivity, whereas certain Treg cell clones were developmentally linked to several T helper (TH) cell clones. Notably, we identified two IFNG+ TH1-like cell clusters in tumours that were associated with distinct IFNγ-regulating transcription factors —the GZMK+ effector memory T cells, which were associated with EOMES and RUNX3, and CXCL13+BHLHE40+ TH1-like cell clusters, which were associated with BHLHE40. Only CXCL13+BHLHE40+ TH1-like cells were preferentially enriched in patients with microsatellite-instable tumours, and this might explain their favourable responses to immune-checkpoint blockade. Furthermore, IGFLR1 was highly expressed in both CXCL13+BHLHE40+ TH1-like cells and CD8+ exhausted T cells and possessed co-stimulatory functions. Our integrated STARTRAC analyses provide a powerful approach to dissect the T cell properties in colorectal cancer comprehensively, and could provide insights into the dynamic relationships of T cells in other cancers.
Suggested Citation
Lei Zhang & Xin Yu & Liangtao Zheng & Yuanyuan Zhang & Yansen Li & Qiao Fang & Ranran Gao & Boxi Kang & Qiming Zhang & Julie Y. Huang & Hiroyasu Konno & Xinyi Guo & Yingjiang Ye & Songyuan Gao & Shan , 2018.
"Lineage tracking reveals dynamic relationships of T cells in colorectal cancer,"
Nature, Nature, vol. 564(7735), pages 268-272, December.
Handle:
RePEc:nat:nature:v:564:y:2018:i:7735:d:10.1038_s41586-018-0694-x
DOI: 10.1038/s41586-018-0694-x
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