Name
Abstract | ||
|---|---|---|
T cells are key elements of cancer immunotherapy(1) 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-antigens(2), could serve as lineage tags to track these T cells in tumours(3). 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 (T-reg) cells showed clonal exclusivity, whereas certain T-reg cell clones were developmentally linked to several T helper (T-H) cell clones. Notably, we identified two IFNG(+) T(H)1-like cell clusters in tumours that were associated with distinct IFN gamma-regulating transcription factors-the GZMK(+) effector memory T cells, which were associated with EOMES and RUNX3, and CXCL13(+) BHLHE40(+) T(H)1-like cell clusters, which were associated with BHLHE40. Only CXCL13(+) BHLHE40(+) T(H)1-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(+) T(H)1-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. |
Year | DOI | Venue |
|---|---|---|
2018 | 10.1038/s41586-018-0694-x | NATURE |
DocType | Volume | Issue |
Journal | 564 | 7735 |
ISSN | Citations | PageRank |
0028-0836 | 1 | 0.41 |
References | Authors | |
5 | 20 | |
Name | Order | Citations | PageRank |
|---|---|---|---|
| Lei Zhang | 1 | 1 | 0.75 |
| Xin Yu | 2 | 1 | 0.41 |
| Liangtao Zheng | 3 | 1 | 0.41 |
| Yuanyuan Zhang | 4 | 1 | 0.41 |
| Yansen Li | 5 | 1 | 0.41 |
| Qiao Fang | 6 | 1 | 0.41 |
| Ranran Gao | 7 | 1 | 0.41 |
| Boxi Kang | 8 | 10 | 1.69 |
| Qiming Zhang | 9 | 2 | 0.84 |
| Julie Y Huang | 10 | 1 | 0.41 |
| Hiroyasu Konno | 11 | 1 | 0.41 |
| Xinyi Guo | 12 | 1 | 0.41 |
| J Ying | 13 | 3 | 1.75 |
| Songyuan Gao | 14 | 1 | 0.41 |
| Shan Wang | 15 | 1 | 0.41 |
| Xueda Hu | 16 | 2 | 1.03 |
| Xian-Wen Ren | 17 | 33 | 3.99 |
| Zhanlong Shen | 18 | 1 | 0.41 |
| Wenjun Ouyang | 19 | 1 | 0.41 |
| Zemin Zhang | 20 | 50 | 6.46 |