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Lineage tracking reveals dynamic relationships of T cells in colorectal cancer
- Source :
- Nature. 564:268-272
- Publication Year :
- 2018
- Publisher :
- Springer Science and Business Media LLC, 2018.
-
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. An integrated RNA-sequencing approach demonstrates that CXCL13+ TH1-like cells are preferentially enriched in microsatellite-instable tumours from patients with colorectal cancer, and IGFLR1 is identified as a co-stimulatory molecule.
- Subjects :
- CD4-Positive T-Lymphocytes
0301 basic medicine
T cell
Cell
CD8-Positive T-Lymphocytes
Biology
Transcriptome
03 medical and health sciences
Cell Movement
medicine
Humans
Cell Lineage
CXCL13
Cells, Cultured
Adaptor Proteins, Signal Transducing
Multidisciplinary
Effector
T-cell receptor
Cancer
Th1 Cells
medicine.disease
Clone Cells
Cell biology
030104 developmental biology
medicine.anatomical_structure
Cell Tracking
Carrier Proteins
Colorectal Neoplasms
CD8
Subjects
Details
- ISSN :
- 14764687 and 00280836
- Volume :
- 564
- Database :
- OpenAIRE
- Journal :
- Nature
- Accession number :
- edsair.doi.dedup.....053b87d7752b811a322ba95e2315e46a