Zhuang Jing, Qu Zhanbo, Chu Jian, Wang Jingjing, Wu Yinhang, Fan Zhiqing, Song Yifei, Han Shuwen, Ru Lixin, Zhao Hui
Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, China.
Fifth Affiliated Clinical Medical College of Zhejiang Chinese Medical University, Huzhou Central Hospital, China.
Heliyon. 2023 Jul 5;9(7):e17119. doi: 10.1016/j.heliyon.2023.e17119. eCollection 2023 Jul.
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.
细胞介导的免疫逃逸是一种微环境因素，可诱导肿瘤发生和转移。本研究的目的是展示免疫微环境中T细胞群体在结直肠癌（CRC）转移中的特征。进行无监督聚类分析，以从外周血中的3003个细胞和组织中的4656个细胞中识别功能不同的T细胞簇。随后，分别从肿瘤组织和外周血中鉴定出总共8个和4个不同的T细胞群体簇。组织中的高水平CD8 + TEX、CD4 + TRM、TH1样T细胞、CD8 + TEM、肿瘤Treg以及外周血中的CD4 + TN是预测CRC转移的免疫微环境的重要组成部分。此外，耗竭性T细胞的特征是多种抑制性受体的表达较高，包括PDCD1和LAG3。簇状T细胞中的一些基因，如PFKFB3、GNLY、circDCUN1D4、TXNIP和NR4A2，在CRC转移和非转移之间存在统计学差异。不同簇细胞之间鉴定出的配体-受体相互作用以及从每个簇中鉴定出的转移相关差异表达基因表明，细胞通讯、功能改变和T亚群数量可能有助于CRC的转移。转移性CRC中组织T细胞中KiAA1551、ATP8B4和LNPEP以及外周血中SOR1的突变频率高于非转移性CRC。总之，T细胞中差异基因的发现可能为CRC转移的免疫治疗提供潜在靶点，并为CRC转移的临床预测和预后提供相关见解。
