Epigenetic abnormalities of classical Hodgkin lymphoma and its effect on immune escape

Cell Biochem Funct. 2020 Apr;38(3):242-248. doi: 10.1002/cbf.3463. Epub 2019 Nov 11.

Abstract

Classical Hodgkin lymphoma (cHL) is a particular kind of malignant tumour that originates from the B cells. The malignant phenotype of cHL is, at least in part, maintained by epigenetic aberrations, which primarily consist of abnormal histone methylation and acetylation. Progress has been made in clinical trials concerning the histone deacetylases inhibitors (HDACis) in cHL. Also, some demethylation regimens could serve the purpose of preventing and treating tumours. Programmed death-ligand receptor 1 (PD-L1, CD274) inhibitors or apoptosis receptor 1 (PD-1, CD279) inhibitors are used in treating patients with relapsed cHL in recent years. Academic researches indicated that PD-1/PD-L1 inhibitors, including nivolumab and pembrolizumab, demonstrate remarkable activity in relapsed cHL. In addition, in recent years, a close association between epigenetic aberrations and immune escape has been explored in cHL. DNA methyltransferase (DNMT) inhibitors, HDACis, and immune checkpoint blockade exhibit synergistic effects. Thus, this review aims to provide an overview on the epigenetic abnormalities of cHL and its effect on immune escape, in order to explore the optimal combination approach to treat the disease. SIGNIFICANCE OF THE STUDY: Cancer Statistics 2018 reported that more than 8000 new cases of Hodgkin lymphoma were diagnosed. In recent years, PD-1/PD-L1 inhibitors for cHL have been utilized, and the therapeutic strategies of HDACis combined with PD-1/PD-L1 inhibitors have been raised. It is critical for improving the efficacy and decreasing the toxicity in treating the patients with cHL.

Keywords: acetylation; classical Hodgkin lymphoma; histone deacetylases inhibitors; immune checkpoint inhibitors; immune escape; methylation.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis
  • B7-H1 Antigen / antagonists & inhibitors
  • CpG Islands
  • DNA (Cytosine-5-)-Methyltransferase 1 / antagonists & inhibitors
  • DNA Methylation
  • Enzyme Inhibitors / pharmacology
  • Epigenesis, Genetic*
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Gene Silencing
  • Hodgkin Disease / genetics*
  • Hodgkin Disease / immunology*
  • Humans
  • Phenotype
  • Tumor Escape*

Substances

  • Antineoplastic Agents
  • B7-H1 Antigen
  • CD274 protein, human
  • Enzyme Inhibitors
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNMT1 protein, human