The role of HLA-G for protection of human renal cell-carcinoma cells from immune-mediated lysis: implications for immunotherapies.
HLA-G as a non-classical MHC class I molecule exhibits a limited tissue distribution and exerts multiple immune regulatory functions including the induction of immune tolerance. In addition, HLA-G has been detected in some tumors of different histology and therefore may represent a novel immune escape mechanism of tumor cells. Despite the immunogenicity of renal cell carcinoma (RCC), outgrowth of tumor cells occurs which might be attributable to abrogation of efficient anti-tumor responses. We here review the potential role of HLA-G in RCC immunology, the HLA-G expression pattern and its functional consequences on immune responses. A heterogenous constitutive and interferon-gamma inducible HLA-G mRNA and protein expression was found in RCC cell lines and tumor lesions, but not in autologous normal kidney epithelium. HLA-G transcription and protein expression was detected at a high frequency in primary RCC lesions and RCC cell lines. Functional studies performed with alloreactive natural and lymphokine activated killer cells as well as antigen-specific CD8+ T cell populations demonstrated that HLA-G expression inhibits lysis of RCC cells by these different immune effector cells, whereas HLA-G- normal kidney cells were recognized. Thus, aberrant HLA-G expression might participate in evasion of these tumor cells from immunosurveillance.
Bukur
Jürgen
J
Illrd Department of Internal Medicine, Johannes Gutenberg University, Langenbeckstr 1, 55101 Mainz, Germany.
Seliger
Barbara
B
D002292:Carcinoma, Renal Cell / Q000276:immunology* / Q000628:therapy*; D005434:Flow Cytometry; D006680:HLA Antigens / Q000096:biosynthesis / Q000502:physiology*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000502:physiology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D007680:Kidney Neoplasms / Q000276:immunology* / Q000628:therapy*; D012333:RNA, Messenger / Q000378:metabolism
D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D012333:RNA, Messenger; D007371:Interferon-gamma