Programmed Cell Death 1 and Hepatocellular Carcinoma: An Epochal Story

J Gastrointest Cancer. 2021 Dec;52(4):1217-1222. doi: 10.1007/s12029-021-00758-z. Epub 2021 Dec 11.

Abstract

In recent years, immune-based therapies have emerged as novel pillars for hepatocellular carcinoma (HCC). The rationale of immune-checkpoint inhibitors (ICIs) trial in HCC originated from the fact that the tumor cells and the infiltrating stromal and immune cells promote an immunosuppressive tumor microenvironment, including the up-regulation of immune checkpoint molecules on their surface. Antibody-based blockage targeting inhibitory checkpoint molecules on cytotoxic T cells, including programmed cell death-1 (PD-1) or its counterpart on antigen-presenting cells has shown strong anti-tumor activity in a subset of HCC patients. Single nucleotide polymorphisms (SNP) of PD-1 gene may affect the PD-1 expression or function, which eventually can cause dysfunctionality of immune balance. Based on the inhibitory role of PD-1 in anti-tumor responses, it has been investigated in several studies as a candidate to test for genetic susceptibility of individuals to HCC. The present paper highlights the knowledge on cross-talks for liver immunology and HCC course, recent studies investigating the role of functional SNPs of PD-1 gene in Turkish HCC population, and the data on already investigated PD-1 inhibitor molecules in clinical trials.

Keywords: Hepatocellular carcinoma; Immune-checkpoint inhibitor; Programmed cell death-1; Single nucleotide polymorphism.

Publication types

  • Review

MeSH terms

  • Apoptosis
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Humans
  • Immune Checkpoint Inhibitors / pharmacology*
  • Immunotherapy
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Polymorphism, Single Nucleotide
  • Programmed Cell Death 1 Receptor / drug effects
  • Programmed Cell Death 1 Receptor / genetics*
  • Turkey

Substances

  • Immune Checkpoint Inhibitors
  • Programmed Cell Death 1 Receptor