HLA-G and immune evasion in cancer cells.
Acquisition of novel gene products or new antigens in cancer cells elicits a host immune response that results in selection pressure for tumor clones to evade immunosurveillance. Similar to maternal-fetal tolerance and allotransplantation acceptance, upregulation of HLA-G expression has been found as one of the mechanisms that are programmed in cancer cells. HLA-G expression is frequently detected in a wide variety of human cancers and its protein levels negatively correlate with poor clinical outcome. The immune inhibitory effect can be achieved by binding of HLA-G molecules to the immunoglobulin-like inhibitory receptors that are expressed on the immunocompetent cells at all stages of the immune response. This review summarizes recent studies of HLA-G expression in human cancer, with a special focus on the molecular mechanisms that underlie how HLA-G molecules facilitate tumor cell evasion of the host immune response, and presents new directions for developing HLA-G-based diagnosis/therapeutics.
Sheu
Jim
J
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21231, USA.
Shih
Ie-Ming
IeM
D015972:Gene Expression Regulation, Neoplastic; D006680:HLA Antigens / Q000378:metabolism*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D057131:Immune Evasion; D007121:Immunocompetence / Q000235:genetics / Q000276:immunology; D015166:Monitoring, Immunologic; D009369:Neoplasms / Q000276:immunology
D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I