Single-cell RNA-seq Revealed that Altered Tumor Infiltrating Lymphocytes in Cirrhotic Liver Indicate Development of Hepatocellular Carcinoma  

作　　者：Jingxian Duan Peng Zhu Yong Zhang Tianhao Mu Yingqiang Li Rui Xiong Su Chen Yingmei Li Zhicheng Li Shifu Chen Lei Zhang 

机构地区：[1]Shenzhen Institutes of Advanced Technology,Chinese Academy of Sciences,Shenzhen,Guangdong,China [2]Hepatic Surgery Center,Tongji Hospital,Huazhong University of Science and Technology,Wuhan,Hubei,China [3]Department of Hepatobiliary Surgery,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei,China [4]HaploX Biotechnology Co.Ltd,Shenzhen,Guangdong,China [5]Hepatopancreatobiliary Surgery,Hubei Cancer Hospital,Wuhan,Hubei,China [6]Department of Hepatobiliary Surgery,Shanxi Bethune Hospital,Shanxi Academy of Medical Sciences,Shanxi Medical University,Shanxi Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Taiyuan,Shanxi,China [7]Key Laboratory of Hepatobiliary and Pancreatic Diseases of Shanxi Province(Preparatory),Shanxi Bethune Hospital,Shanxi Academy of Medical Sciences,Shanxi Medical University,Shanxi Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Taiyuan,Shanxi,China

出　　处：《Journal of Clinical and Translational Hepatology》2023年第4期850-862,共13页临床与转化肝病杂志（英文版）

基　　金：This study received financial support from the Key-Area Research and Development Program of Guangdong Province(No.2021B0101420006);the National Natural Science Foundation of China(Nos.62201557,U20A20171,12126608,82073090);the Shenzhen Science and Technology Innovation Committee Technical Research Projects(Nos.JSGG20180703164202084,KQJSCX20180330124428928,JSGG20180508152646606);the Guangdong Basic and Applied Basic Research Foundation(Nos.2020B1515120046,2021A1515110585);Shanxi Province“136”Revitalization Medical Project Construction Funds.

摘　　要：Background and Aims:Cirrhosis is the precursor lesion for most hepatocellular carcinoma(HCC)cases.However,no biomarker effectively predicted HCC initiation before diagnosis by imaging.We aimed to investigate the hallmarks of immune microenvironments in healthy,cirrhotic livers and HCC tumor tissues and to identify immune biomarkers of cirrhosis-HCC transition.Methods:Expression matrices of singlecell RNA sequencing studies were downloaded and integrated with Seurat package vignettes.Clustering was performed to analyze the immune cell compositions of different sample types.Results:The cirrhotic liver and HCC tumors had distinct immune microenvironments,but the immune landscape of cirrhotic livers was not markedly modified compared with healthy livers.Two subsets of B cells and three subsets of T cells were identified in the samples.Among the T cells,naïve T cells were more prominent in the cirrhotic and healthy liver samples than in the HCC samples.In contrast,the neutrophil count was lower in cirrhotic livers.Two macrophage clusters were identified,one that actively interacted with T cells and B cells and was enriched in cirrhotic blood compared with HCC blood samples.Conclusions:Decreased naïve T cell infiltration and increased neutrophil infiltration in the liver may indicate the development of HCC in cirrhotic patients.Alterations in blood-resident immune cells may also be a sign of HCC development in cirrhotic patients.The dynamics of the immune cell subsets may serve as novel biomarkers to predict the transition from cirrhosis to HCC.

关 键 词：Immune microenvironment Single-cell RNA sequencing CIRRHOSIS Hepatocellular carcinoma LIVER 

分 类 号：R735.7[医药卫生—肿瘤]