Role of HLA-G in tumor escape through expansion of myeloid-derived suppressor cells and cytokinic balance in favor of Th2 versus Th1/Th17

Blood. 2011 Jun 30;117(26):7021-31. doi: 10.1182/blood-2010-07-294389. Epub 2011 Apr 11.


The expression of HLA-G by malignant cells has been proposed as a tumor escape mechanism from immunosurveillance. However, although the inhibitory effect of HLA-G on antitumoral immune effectors has been documented in vitro, it remains to be resolved in vivo. In this context, the development of an animal model is now a priority to establish the proof of concept that an HLA-G(+) tumor cell develops and tolerizes the host antitumor immune response in vivo. In the present study, we provide the first in vivo evidence of such a role by a xenotumor model in mice based on the interactions between human HLA-G and the murine paired immunoglobulin-like receptor-B (PIR-B). We demonstrate that human tumor cells expressing HLA-G grow in an immunocompetent host by affecting both innate and adaptive immunity. Expansion of blood myeloid-derived CD11b(+)Gr1(+)PIR-B(+) suppressor cells, loss of peripheral T cells, and cytokinic balance in favor of Th2 versus Th1/Th17 constitute the main mechanisms by which HLA-G promotes tumor expansion. These data demonstrate for the first time that HLA-G plays a crucial role in in vivo tumor evasion. Finally, blocking HLA-G function by a specific Ab inhibits the in vivo development of the tumor, offering a new innovative therapeutic strategy in cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Animals
  • Antigens, Neoplasm / chemistry
  • Antigens, Neoplasm / metabolism
  • Cell Line, Tumor
  • Cell Proliferation*
  • Cytokines / metabolism
  • Female
  • HLA Antigens / chemistry
  • HLA Antigens / genetics
  • HLA Antigens / immunology*
  • HLA Antigens / metabolism
  • HLA-G Antigens
  • Histocompatibility Antigens Class I / chemistry
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / immunology*
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Immunity, Innate
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Mice
  • Mice, Inbred Strains
  • Monitoring, Immunologic*
  • Myeloid Cells / immunology*
  • Myeloid Cells / metabolism
  • Neoplasm Transplantation
  • Neoplasms / immunology*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Protein Isoforms / antagonists & inhibitors
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Receptors, Immunologic / metabolism
  • Th1-Th2 Balance
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism
  • Tumor Escape*


  • Antigens, Neoplasm
  • Cytokines
  • HLA Antigens
  • HLA-G Antigens
  • Histocompatibility Antigens Class I
  • Pirb protein, mouse
  • Protein Isoforms
  • Receptors, Immunologic