INVESTIGADORES
ZWIRNER Norberto Walter
congresos y reuniones científicas
Título:
BENIGN QUIESCENT MELANOCYTIC NEVI DO NOT EXPRESS THE NK CELL ACTIVATING LIGAND MICA (MHC CLASS I-RELATED CHAIN GENE A)
Autor/es:
CABRERA, HUGO; ALLEVATO, MIGUEL; PERALTA, CARLOS; FUERTES, MERCEDES BEATRIZ; ZWIRNER, NORBERTO WALTER
Lugar:
Buenos Aires
Reunión:
Congreso; 21th World Congress of Dermatology; 2007
Institución organizadora:
International League of Dermatology Societies
Resumen:
Natural killer (NK) cells are critical players during tumor growth control in immunocompetent hosts. Their function is achieved through recognition of specific cell surface molecules by activating receptors. The most thoroughly characterized of such receptors is a molecule called NKG2D. This receptor directs the tumoricidal activity of the NK cells against tumor cells that express a group of ligands (NKG2DLs) such as MICA (MHC class I-related chain A gene). It has been extensively documented in the literature that MICA is broadly expressed on tumors of different histotypes (in particular, melanomas), for which its expression has been associated with the phenomenon of neotransformation. Recently, it was demonstrated that it is actually the DNA damage response what triggers MICA expression in response to genotoxic stimuli. In spite of these observations, most tumors grow in immunocompetent hosts despite expressing significant amounts of NKG2DLs. This apparent paradox is explained by the recent description of some tumor immune escape mechanisms that compromise the MICA-NKG2D system. However, nothing is known about the expression of MICA in benign, preneoplasic pathologies. In this study, we performed an analysis of the expression of MICA on the cell surface of 14 benign quiescent melanocytic nevi obtained from untreated patients that attended to our Dermatology Unit. Samples were selected according to the clinical diagnosis and dermatoscopic analysis and the diagnosis of benign quiescent melanocytic nevi was confirmed by the pathologist. Surface expression of MICA was analyzed by flow cytometry with a locally-produced specific monoclonal antibody. We observed that none of the 14 samples analyzed exhibited surface MICA expression. On the contrary, many different human melanoma-derived cell lines and even a grade II/III, freshly isolated human melanoma showed high surface expression of this NKG2DL. In addition, when the sample size was enough to prepare cell lysates and perform Western blot analysis (in 3 cases), we observed that these benign quiescent melanocytic nevi did not show MICA expression, in opposition of what was observed in melanoma-derived cell lines and the grade II/III, freshly isolated human melanoma. Therefore, our results indicate that neo-expression of MICA is an event that takes place after the cell achieved the malign transformation into a melanoma, a characteristic that would confer susceptibility to NK cell-mediated cytotoxicity. Thus, benign quiescent melanocytic nevi would be protected from such immunosurveillance. The results here described represent the first analysis of expression of MICA in benign melanocytic nevi.