Single-cell analysis revealed a potential role of T-cell exhaustion in colorectal cancer with liver metastasis

Tianlong Ling ¹, Cheng Zhang ¹, Ye Liu ¹

⁰Department of Gastrointestinal Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Journal of Cellular and Molecular Medicine +

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April 22, 2024

View abstract on PubMed

Summary

T-cell exhaustion promotes liver metastasis in colorectal cancer (CRC). Exhausted T cells (Tex) drive tumor development, offering new diagnostic and treatment strategies for CRC liver metastasis.

Area Of Science

Oncology
Immunology
Genomics

Background

Liver metastasis (LM) significantly contributes to colorectal cancer (CRC) mortality.
The role of T-cell exhaustion in CRC liver metastasis remains largely undefined.

Purpose Of The Study

To investigate the impact of T-cell exhaustion on liver metastasis in colorectal cancer.
To elucidate the cellular dynamics and interactions driving CRC progression to LM.

Main Methods

Single-cell RNA sequencing data analysis using Seurat.
Pseudo-time analysis for cell differentiation trajectories.
Single-sample gene set enrichment analysis (ssGSEA) and cell communication analysis.

Main Results

Identified nine cell subpopulations in CRC with LM, noting an increase in T cells, including exhausted T cells (Tex).
Promoted cell adhesion and proliferation of Tex cells in LM.
Revealed CEACAM5 and ADGRE5-CD55 mediated interactions between Tex, Treg, and epithelial cells, potentially driving epithelial-mesenchymal transition.

Conclusions

T-cell exhaustion plays a critical role in promoting liver metastasis in colorectal cancer.
Tex cells contribute to tumor development and progression in CRC.
Findings offer novel perspectives for the diagnosis and treatment of CRC liver metastasis.

Keywords:

exhausted T cells liver metastasis primary colorectal cancer regulatory T cells single‐cell sequencing