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
Affiliations
Jing Zhuang
Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, China; Fifth Affiliated Clinical Medical College of Zhejiang Chinese Medical University, Huzhou Central Hospital, China; Key Laboratory of Multiomics Research and Clinical Transformation of Digestive Cancer of Huzhou, China
Zhanbo Qu
Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, China; Fifth Affiliated Clinical Medical College of Zhejiang Chinese Medical University, Huzhou Central Hospital, China; Key Laboratory of Multiomics Research and Clinical Transformation of Digestive Cancer of Huzhou, China
Jian Chu
Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, China; Fifth Affiliated Clinical Medical College of Zhejiang Chinese Medical University, Huzhou Central Hospital, China; Key Laboratory of Multiomics Research and Clinical Transformation of Digestive Cancer of Huzhou, China
Jingjing Wang
Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, China
Yinhang Wu
Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, China; Fifth Affiliated Clinical Medical College of Zhejiang Chinese Medical University, Huzhou Central Hospital, China; Key Laboratory of Multiomics Research and Clinical Transformation of Digestive Cancer of Huzhou, China
Zhiqing Fan
Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, China
Yifei Song
Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, China
Shuwen Han
Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, China; Fifth Affiliated Clinical Medical College of Zhejiang Chinese Medical University, Huzhou Central Hospital, China; Key Laboratory of Multiomics Research and Clinical Transformation of Digestive Cancer of Huzhou, China
Lixin Ru
Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, China; Fifth Affiliated Clinical Medical College of Zhejiang Chinese Medical University, Huzhou Central Hospital, China; Key Laboratory of Multiomics Research and Clinical Transformation of Digestive Cancer of Huzhou, China
Hui Zhao
Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, China; Fifth Affiliated Clinical Medical College of Zhejiang Chinese Medical University, Huzhou Central Hospital, China; Key Laboratory of Multiomics Research and Clinical Transformation of Digestive Cancer of Huzhou, China; Corresponding author. No.1558, Sanhuan North Road, Wuxing District, Huzhou, Zhejiang Province, 313000, China.
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.
