Expression of tolerogenic HLA-G molecules in cancer prevents antitumor responses

Semin Cancer Biol. 2007 Dec;17(6):413-21. doi: 10.1016/j.semcancer.2007.07.003. Epub 2007 Jul 17.

Abstract

In this paper, we focus our attention on the relevance of HLA-G in cancer in the light of our recent advances on the expression and immunological function of HLA-G. Regarding HLA-G function, we recently showed that in addition to its direct inhibitory effects on T, APC and NK function, HLA-G induces suppressor cells via two distinct processes: (i) either by cell differentiation of naïve T cells into lasting suppressor T cells or (ii) by rapid transfer of HLA-G from APC or tumor cells to T or NK cells converting them into temporary HLA-G-positive suppressor cells. Regarding HLA-G expression, we described that tumor-microenvironment factors such as hypoxia, IDO and, TNF-alpha regulate the expression of HLA-G by tumor cells in a way that favors tumor escape from NK lysis. These findings reinforce the role of HLA-G as one mechanism of tumor-driven immune evasion and provide potential targets for testing novel anticancer treatment strategies.

Publication types

  • Review

MeSH terms

  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Hypoxia
  • HLA Antigens / immunology*
  • HLA Antigens / metabolism
  • HLA-G Antigens
  • Histocompatibility Antigens Class I / immunology*
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Immunologic Surveillance
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Neoplasms / immunology*
  • Neoplasms / metabolism
  • Protein-Serine-Threonine Kinases / metabolism
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • Tumor Escape*

Substances

  • HLA Antigens
  • HLA-G Antigens
  • Histocompatibility Antigens Class I
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Protein-Serine-Threonine Kinases
  • NF-kappa B kinase