HLA-G in melanoma: A new strategy to escape from immunosurveillance?
The non-classical HLA class-I molecule HLA-G, primarily expressed on fetal cells of the human placenta, has been shown to play a crucial role in maintaining an immuno-privileged environment at the materno-fetal interface. Fetal trophoblast cells are protected from attack by CD8+ cytotoxic T lymphocytes due to their lacking expression of classical HLA class-I molecules, again rendering them susceptible to natural killer (NK) cell lysis. HLA-G has been shown to interact with killing inhibitory receptors, hereby rescuing the fetal placenta cells from NK cell attack. Likewise, classical HLA class-I molecules are known to be frequently downregulated or lost during the development of malignancies. This abnormality is often associated with a poor clinical course of disease, despite of the frequent detection of tumor-infiltrating NK cells. This controversy seemed to be resolved with the detection of HLA-G expression on cells of malignant melanoma and other solid tumors. Since interferon(IFN)s are known for their ability of upregulation or induction of HLA-G expression, the potential function of HLA-G as a new strategy of cancer cells to escape from immunosurveillance might be of particular importance in malignant melanoma. The frequent use of IFN-alpha in the immunotherapy of this malignancy might possibly worsen the already impaired antitumoral immune response state of melanoma patients. However, several studies recently failed to detect any HLA-G protein expression in cancer cell lines and tissues of different origin, particularly in malignant melanoma, yet rendering the expression and function of HLA-G in malignancies as a possibly overrated matter of controversial debate.
Ugurel
S
S
Department of Dermatology, The Saarland University Hospital, Homburg/Saar, Germany. selma.ugurel@uniklinik-saarland.de
Reinhold
U
U
Tilgen
W
W
D006680:HLA Antigens / Q000502:physiology*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D006801:Humans; D007157:Immunologic Surveillance / Q000276:immunology; D007167:Immunotherapy; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use; D008545:Melanoma / Q000188:drug therapy / Q000276:immunology*; D011379:Prognosis; D012878:Skin Neoplasms / Q000188:drug therapy / Q000276:immunology*; D019139:Tumor Escape / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology
D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D016898:Interferon-alpha