HLA-G: A New Immune Checkpoint in Cancer?

Int J Mol Sci. 2020 Jun 25;21(12):4528. doi: 10.3390/ijms21124528.

Abstract

Human leukocyte antigen G (HLA-G), known as a central protein in providing immune tolerance to the fetus in pregnant women, is also studied for a possible role in tumor development. Many studies have claimed HLA-G as a new immune checkpoint in cancer. Therefore, HLA-G and its receptors might be targets for immune checkpoint blockade in cancer immunotherapy. In order to substantiate that HLA-G is indeed an immune checkpoint in cancer, two important questions need to be answered: (1) To what extent is HLA-G expressed in the tumor by cancer cells? and (2) What is the function of HLA-G in cancer immune evasion? In this review, we discuss these questions. We agree that HLA-G is a potentially new immune checkpoint in cancer, but additional evidence is required to show the extent of intra-tumor and inter-tumor expression. These studies should focus on tumor expression patterns of the seven different HLA-G isoforms and of the receptors for HLA-G. Furthermore, specific roles for the different HLA-G isoforms should be established.

Keywords: HLA-G; cancer; immune checkpoint; immunotherapy.

Publication types

  • Editorial
  • Review

MeSH terms

  • HLA Antigens / genetics
  • HLA Antigens / immunology
  • HLA Antigens / metabolism
  • HLA-G Antigens / genetics
  • HLA-G Antigens / immunology*
  • HLA-G Antigens / metabolism*
  • Humans
  • Immune Evasion / immunology
  • Immune Tolerance / immunology
  • Immunotherapy / methods
  • Immunotherapy / trends
  • Neoplasms / immunology*
  • Protein Isoforms / metabolism

Substances

  • HLA Antigens
  • HLA-G Antigens
  • Protein Isoforms