Blocking Tim-3 or/and PD-1 reverses dysfunction of tumor-infiltrating lymphocytes in HBV-related hepatocellular carcinoma

Furong Liu, Gucheng Zeng, Shaotang Zhou, Xiaoshun He, Nianfeng Sun, Xiaofeng Zhu, Anbin Hu

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Background: The immunosuppression of tumor-infiltrating lymphocytes (TILs) is associated with rapid progression of hepatitis B virus-related hepatocellular carcinoma (HBV-HCC). T cell Ig- and mucin-domain-containing molecule-3 (Tim-3) and programmed cell death 1 (PD-1) are important inhibitory molecules expressed on the surface of T cells, but their roles in the function of TILs in HBV-HCC are poorly understood. We aimed to study the roles of these two markers in HBV-HCC. Methods: Ninety patients with pathologically confirmed HBV-associated HCC were enrolled in our study. Blood samples, paired fresh tumor tissues and adjacent tissues were collected, and isolating peripheral blood mononuclear cells, TILs and adjacent-infiltrating lymphocytes were isolated from these samples. The patients were followed-up to allow survival analysis. Results: Tim-3 or/and PD-1 was up-regulated expressed on CD4+ and CD8+ TILs in HBV-HCC patients and a higher proportion of TILs expressed PD-1 alone. Tim-3+ and PD-1+ TILs greatly decreased secretion of IFN-? and TNF-a. Expression of Tim-3 and PD-1 on TILs negatively correlated with disease-free survival of HCC patients. Direct blockade of Tim-3 and PD-1 in vitro significantly enhanced TILs proliferation and secretion of IFN-? and TNF-a. Conclusion: Expression of Tim-3 and/or PD-1 on TILs impairs their function and correlates negatively with disease-free survival in HBV-HCC. Direct blockade of Tim-3 and PD-1 restores anti-tumor effects of TILs, which suggests a potential target for novel immunotherapy in HBV-HCC.

Original languageEnglish (US)
Pages (from-to)493-501
Number of pages9
JournalBulletin du Cancer
Volume105
Issue number5
DOIs
StatePublished - May 2018

Keywords

  • HBV: hepatocellular carcinoma
  • PD-1 (Programmed cell death 1)
  • TILs
  • TIM3 (T cell Ig- and mucin-domain-containing molecule-3)

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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