Heterogeneity of HLA-G gene transcription and protein expression in malignant melanoma biopsies

Nonclassical MHC class I HLA-G antigen expression is tissue specific and is thought to play a role in tolerance of the semiallogeneic fetus by the mat ernal immune system. Ectopic expression of HLA-G by tumor cells provides th em with an additional mechanism of escape from immunosurveillance by host c ytotoxic effector mechanisms, The aim of this study eras to assess the expr ession of nonclassical HLA-G antigens in ex vivo human melanoma biopsies. H LA-G mRNA levels corresponding to both membrane-bound and soluble protein i soforms were analyzed in tumor specimens obtained from primary or metastati c melanomas of 23 patients. High levels of ALA-G transcription were detecte d in tumor specimens in 5 of 23 patients and found to be comparable in both lymph node and skin metastases, HLA-G mRNA transcript levels at tumor site s in 18 of these patients were compared with those in samples of their own healthy shin and were higher in the tumor tissue in 12 patients, Differenti al expression of mRNA transcripts corresponding to soluble and membrane-bou nd HLA-G was also observed in some tumor biopsies. HLA-G protein expression was detected in tumors that exhibited high levels of HLA-G transcription by immunofluorescence of frozen sections and Western blot analysis of both tumor and healthy skin biopsies, using anti-HLA-G-sp ecific monoclonal antibodies, This work provides evidence that HLA-G gene t ranscription and protein expression can be up-regulated ex vivo in melanoma , Our finding that several of the tumors studied expressed high levels of H LA-G provides additional clues as to how a tumor can be selected in vivo to escape from cytotoxic antitumor responses, constituting a new parameter to be considered in the design of therapeutic approaches aimed at enhancing a ntitumor immune responses.