title: High-throughput T cell receptor sequencing reveals distinct repertoires between tumor and adjacent non-tumor tissues in HBV-associated HCC.
abstract: T lymphocytes, which recognize antigen peptides through specific T cell receptors (TCRs), play an important role in the human adaptive immune response. TCR diversity is closely associated with host immune response and cancer prognosis. Although tumor-infiltrating T lymphocytes have implications for tumor prognosis, few studies have performed a detailed characterization of TCR diversity in both tumor and non-tumor tissues in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). Here, we performed high-throughput sequencing of the TCRβ chain complementarity determining region 3 (CDR3) of liver-infiltrating T cells from 48 HBV-associated HCC patients. A significantly higher average number of CDR3 aa clonotypes (2259 vs. 1324,p< 0.001), and significantly higher TCR diversity (Gini coefficient,p< 0.001; Simpson index,p< 0.01; Shannon entropy,p< 0.001) were observed in tumor tissues compared with adjacent non-tumor tissues. The ratio of highly expanded clones (HECs) was significantly higher in non-tumor tissues than in tumor tissues when the HEC threshold was defined as 2% or greater (p< 0.05). Our analysis of the median Morisita-Horn index indicated weak TCR repertoire similarity between tumor and matched non-tumor tissues. The median number of shared clones in tumor tissue and matched non-tumor tissue from each patient was 360.5, representing 5.1-15.8% (10.6 ± 0.4%) of all clones in each patient. We observed extensive heterogeneity of T lymphocytes in tumors and higher HEC ratios in adjacent non-tumor tissues of HCC patients. The differential T cell repertoires in tumor and non-tumor tissues suggest a distinct T cell immune microenvironment in patients with HBV-associated HCC.
authors.affiliation: Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University , Guangzhou, China.
authors.forename: Yunqing
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University , Guangzhou, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University , Guangzhou, China.
authors.forename: Miaoxian
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University , Guangzhou, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University , Guangzhou, China.
authors.forename: Mingxing
authors.initials: M
authors.lastname: Gong
authors.affiliation: Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University , Guangzhou, China.
authors.forename: Cantao
authors.initials: C
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University , Guangzhou, China.
authors.forename: Hongkai
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University , Guangzhou, China.
authors.forename: Zhanhui
authors.initials: Z
authors.lastname: Wang
keywords: Diversity; T cell receptor; hepatitis B virus; hepatocellular carcinoma; high-throughput sequencing