Single-cell transcriptome analysis reveals T population heterogeneity and functions in tumor microenvironment of colorectal cancer metastases

Jing Zhuang; Zhanbo Qu; Jian Chu; Jingjing Wang; Yinhang Wu; Zhiqing Fan; Yifei Song; Shuwen Han; Lixin Ru; Hui Zhao

doi:10.1016/j.heliyon.2023.e17119

Single-cell transcriptome analysis reveals T population heterogeneity and functions in tumor microenvironment of colorectal cancer metastases

Heliyon. 2023 Jul 5;9(7):e17119. doi: 10.1016/j.heliyon.2023.e17119. eCollection 2023 Jul.

Authors

Jing Zhuang^{1

2

3}, Zhanbo Qu^{1

2

3}, Jian Chu^{1

2

3}, Jingjing Wang¹, Yinhang Wu^{1

2

3}, Zhiqing Fan¹, Yifei Song¹, Shuwen Han^{1

2

3}, Lixin Ru^{1

2

3}, Hui Zhao^{1

2

3}

Affiliations

¹ Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, China.
² Fifth Affiliated Clinical Medical College of Zhejiang Chinese Medical University, Huzhou Central Hospital, China.
³ Key Laboratory of Multiomics Research and Clinical Transformation of Digestive Cancer of Huzhou, China.

Abstract

Cell mediated immune escape, a microenvironment factor, induces tumorigenesis and metastasis. The purpose of this study was to display the characteristics of T cell populations in immune microenvironments for colorectal cancer (CRC) metastasis. Unsupervised cluster analysis was conducted to identify functionally distinct T cell clusters from 3,003 cells in peripheral blood and 4,656 cells in tissues. Subsequently, a total of 8 and 4 distinct T cell population clusters were identified from tumor tissue and peripheral blood, respectively. High levels of CD8+TEX, CD4+TRM, TH1-like T cells, CD8+TEM, tumor-Treg from tissues, and CD4+TN from peripheral blood are essential components of immune microenvironment for the prediction of CRC metastasis. Moreover, exhausted T cells are characterized by higher expression of multiple inhibitory receptors, including PDCD1 and LAG3. Some genes such as PFKFB3, GNLY, circDCUN1D4, TXNIP and NR4A2 in T cells of cluster were statistically different between CRC metastasis and non-metastasis. The ligand-receptor interactions identified between different cluster cells and metastases-related DEGs identified from each cluster revealed that the communications of cells, alterations of functions, and numbers of T subsets may contribute to the metastasis of CRC. The mutation frequency of KiAA1551, ATP8B4 and LNPEP in T cells from tissues and SOR1 from peripheral blood were higher in metastatic CRC than that in non-metastatic CRC. In conclusion, the discovery of differential genes in T cells may provide potential targets for immunotherapy of CRC metastasis and relevant insights into the clinical prediction and prognosis of CRC metastasis.

Keywords: Colorectal cancer; Immune microenvironments; Immunotherapy; Single-cell RNA sequencing; T cell subset.