HLA-G Neo-Expression on Tumors

Front Immunol. 2020 Aug 14:11:1685. doi: 10.3389/fimmu.2020.01685. eCollection 2020.

Abstract

HLA-G is known to modulate the immune system activity in tissues where physiological immune-tolerance is necessary (i.e., maternal-fetal interface, thymus, and cornea). However, the frequent neo-expression of HLA-G in many cancer types has been previously and extensively described and is correlated with a bad prognosis. Despite being an MHC class I molecule, HLA-G is highly present in tumor context and shows unique characteristics of tissue restriction of a Tumor Associated Antigen (TAA), and potent immunosuppressive activity of an Immune CheckPoint (ICP). Consequently, HLA-G appears to be an excellent molecular target for immunotherapy. Although the relevance of HLA-G in cancer incidence and development has been proven in numerous tumors, its neo-expression pattern is still difficult to determine. Indeed, the estimation of HLA-G's actual expression in tumor tissue is limited, particularly concerning the presence and percentage of the new non-canonical isoforms, for which detection antibodies are scarce or inexistent. Here, we summarize the current knowledge about HLA-G neo-expression and implication in various tumor types, pointing out the need for the development of new tools to analyze in-depth the HLA-G neo-expression patterns, opening the way for the generation of new monoclonal antibodies and cell-based immunotherapies.

Keywords: HLA-G; hematopoietic tumors; immune checkpoint; immunotherapy; solid tumors.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use
  • Antigens, Neoplasm / immunology*
  • Antigens, Neoplasm / metabolism
  • Antineoplastic Agents, Immunological / therapeutic use
  • HLA-G Antigens / immunology*
  • HLA-G Antigens / metabolism
  • Humans
  • Immunotherapy, Adoptive
  • Neoplasms / immunology*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Tumor Escape
  • Tumor Microenvironment

Substances

  • Antibodies, Monoclonal
  • Antigens, Neoplasm
  • Antineoplastic Agents, Immunological
  • HLA-G Antigens