Uncovering immune cell heterogeneity in hepatocellular carcinoma by combining single-cell RNA sequencing with T-cell receptor sequencing  

作　　者：Xin-Yu Gu Shuang-Lin Gu Zi-Yi Chen Jin-Long Tong Xiao-Yue Li Hui Dong Cai-Yun Zhang Wen-Xian Qian Xiu-Chang Ma Chang-Hua Yi Yong-Xiang Yi 

机构地区：[1]Department of Infectious Diseases,The Second Hospital of Nanjing,Nanjing University of Chinese Medicine,Nanjing 210003,Jiangsu Province,China [2]Department of General Surgery,Changshu Hospital Affiliated to Nanjing University of Chinese Medicine,Changshu 215500,Jiangsu Province,China [3]Department of Clinical Research Center,The Second Hospital of Nanjing,Nanjing University of Chinese Medicine,Nanjing 210003,Jiangsu Province,China [4]Genetic Center,Reproductive and Genetic Hospital of CITIC-Xiangya,Changsha 410078,Hunan Province,China [5]College of Medical Technology,Shaoyang University,Shaoyang 422000,Hunan Province,China [6]Department of General Surgery,Nanjing Drum Tower Hospital,The Affiliated Hospital of Nanjing University Medical School,Nanjing 210008,Jiangsu Province,China

出　　处：《World Journal of Hepatology》2025年第2期140-158,共19页世界肝病学杂志(英文)

基　　金：Supported by the Scientific Research Topic of Jiangsu Provincial Health Care Commission,No.M2021017;the High-level Talent Research Project of the Second Hospital of Nanjing,No.0313504;the Nanjing Second Hospital Academic Leader Program,No.0313506.

摘　　要：BACKGROUND Understanding the status and function of tumor-infiltrating immune cells is essential for improving immunotherapeutic effects and predicting the clinical response in human patients with carcinoma.However,little is known about tumor-infiltrating immune cells,and the corresponding research results in hepatocellular carcinoma(HCC)are limited.AIM To investigate potential biomarker genes that are important for the development of HCC and to understand how immune cell subsets react throughout this process.METHODS Using single-cell RNA sequencing and T-cell receptor sequencing,the heterogeneity and potential functions of immune cell subpopulations from HCC tissue and normal tissue adjacent to carcinoma,as well as their possible interactions,were analyzed.RESULTS Eight T-cell clusters from patients were analyzed and identified using bioinformatics,including six typical major Tcell clusters and two newly identified T-cell clusters,among which Fc epsilon receptor 1G+T cells were characterized by the upregulation of Fc epsilon receptor 1G,tyrosine kinase binding protein,and T cell receptor delta constant,whereas metallothionein 1E+T cells proliferated significantly in tumors.Differentially expressed genes,such as regulator of cell cycle,cysteine and serine rich nuclear protein 1,SMAD7 and metallothionein 1E,were identified as significantly upregulated in tumors and have potential as biomarkers.In association with T-cell receptor analysis,we inferred the clonal expansion characteristics of each T-cell cluster in HCC patients.CONCLUSION We identified lymphocyte subpopulations and potential biomarker genes critical for HCC development and revealed the clonal amplification of infiltrating T cells.These data provide valuable resources for understanding the response of immune cell subsets in HCC.

关 键 词：Single-cell RNA sequencing Paired T-cell receptor sequencing Hepatocellular carcinoma Immune cell subpopulations Tumor-infiltrating immune cells 

分 类 号：R735.7[医药卫生—肿瘤]