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Genetic and phenotypic difference in CD8+ T cell exhaustion between chronic hepatitis B infection and hepatocellular carcinoma
  1. Xiaochen Wang1,2,
  2. Qifeng He1,2,
  3. Haiyuan Shen1,2,
  4. Xiao-Jie Lu1,2,
  5. Beicheng Sun1
  1. 1 Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
  2. 2 Liver Transplantation Center of the First Affiliated Hospital, Nanjing Medical University, Nanjing, China
  1. Correspondence to Dr Xiao-Jie Lu, Liver Transplantation Center of the First Affiliated Hospital, Nanjing Medical University Nanjing China ; 189{at}whu.edu.cn and Dr Beicheng Sun, Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210009, China; sunbc{at}njmu.edu.cn

Abstract

Background Several recent studies published have suggested that T cell exhaustion exists both in chronic infection and cancer. However, to date, few studies have investigated their differences. Here we designed this study to explore the genetic and phenotypic difference in CD8+ T cell exhaustion between chronic hepatitis B (CHB) and hepatocellular carcinoma (HCC).

Methods In this study, we assayed the phenotypes and functional states of CD8+ T cells separating from human CHB tissues and HCC tissues, and re-analyse the single-cell sequencing data (GSE98638) published previously. Clustering analysis of genes was performed using the T cell exhaustion gene modules (modules 1–4) proposed by Speiseret al.

Results CD8+ T cells from liver tissues of both CHB and HCC showed high levels of exhaustion markers, DOI: programmed cell death-1 (PD-1), T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), and lymphocyte-activation gene 3 (LAG-3), decreased proliferation (Ki67) and cell activity (CD69), and reduced production of effector cytokines (interferon-γ, interleukin-2 and tumour necrosis factor-α). Compared with CD8+ T cells from CHB tissues, those from HCC tissue showed higher expression levels of exhaustion markers, lower levels of proliferation, cell activity and the production of effector cytokines. Cluster analysis showed that exhaustion associated genes in CHB and HCC are inclined to distribute into modules 3 while those isolated from HCC into modules 1 and 2.

Conclusions CD8+ T cell exhaustion existed both in CHB and HCC, but the phenotypes, functional states and underlying mechanisms are somewhat different between the two.

  • chronic hepatitis B
  • Cd8+ T cells
  • T cell exhaustion
  • hepatocellular carcinoma

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Footnotes

  • XW, QH and HS contributed equally.

  • Contributors Conception and design: BS and X-JL. Provision of study materials or patients: XW, QH and HS. Collection and assembly of data: QH and HS. Data analysis and interpretation: XW and QH. Manuscript writing: BS, X-JL and XW. Final approval of manuscript: all authors.

  • Funding This work was supported by grants from the National Key Research and Development Program of China (grant number: 2016YFC0905900 to BS); the State Key Program of National Natural Science Foundation (grant number: 81430062 to BS); Innovative Research Groups of National Natural Science Foundation (grant number: 81521004 to BS), the National Natural Science Foundation (grant number: 81772596 to X-JL) and the Postgraduate EducationReform Project of Jiangsu Province (JX22013394 to X. W).This work was also supported in part by the Priority Academic Program of Jiangsu Higher Education Institutions.

  • Competing interests BS is Yangtze River scholars Distinguished Professor.

  • Patient consent Obtained.

  • Ethics approval Approved by the First Affiliated Hospital of Nanjing Medical University.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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