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Immunology |
DSV-DRM, SRHI/CEA, Commissariat à l’Energie Atomique, Centre Hayem, Hôpital Saint-Louis, 75010 Paris [P. P., F. A. C., I. K-D., C. L. D., E. D. C.]; Laboratoire d’Immunologie des Pathologies Infectieuses et Tumorales, Institut National de la Santé et de la Recherche Médicale U445, Institut Cochin de Génétique Moléculaire, Université René Descartes, 75014 Paris [J-G. G., F-A. L. G.]; Service de Dermatologie, Institut Gustave, 94805 Villejuif cedex [S. M., M-F. A.]; Institut National de la Santé et de la Recherche Médicale U462, Centre Hayem, 75010 Paris [M. S.]; and Fondation Jean Dausset, CEPH, 75010 Paris [J. D.], France
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 maternal immune system. Ectopic expression of HLA-G by tumor cells provides them with an additional mechanism of escape from immunosurveillance by host cytotoxic effector mechanisms. The aim of this study was to assess the expression of nonclassical HLA-G antigens in ex vivo human melanoma biopsies.
HLA-G mRNA levels corresponding to both membrane-bound and soluble protein isoforms were analyzed in tumor specimens obtained from primary or metastatic melanomas of 23 patients. High levels of HLA-G transcription were detected 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 sites in 18 of these patients were compared with those in samples of their own healthy skin and were higher in the tumor tissue in 12 patients. Differential expression of mRNA transcripts corresponding to soluble and membrane-bound 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-specific monoclonal antibodies. This work provides evidence that HLA-G gene transcription and protein expression can be up-regulated ex vivo in melanoma. Our finding that several of the tumors studied expressed high levels of HLA-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 antitumor immune responses.
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