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- Title
Phenotypic and functional changes of human melanoma xenografts induced by DNA hypomethylation: Immunotherapeutic implications.
- Authors
Coral, Sandra; Sigalotti, Luca; Colizzi, Francesca; Spessotto, Alberto; Nardi, Gianpaolo; Cortini, Enzo; Pezzani, Laura; Fratta, Elisabetta; Fonsatti, Ester; di Giacomo, Anna Maria; Nicotra, Maria Rita; Natali, Pier Giorgio; Altomonte, Maresa; Maio, Michele
- Abstract
Emerging in vitro evidence points to an immunomodulatory activity of DNA hypomethylating drugs in human malignancies. We investigated the potential of 5-aza-2′-deoxycytidine (5-AZA-CdR) to modulate the expression of cancer testis antigens (CTA) and of HLA class I antigens by melanoma xenografts, and the resulting modifications in immunogenicity of neoplastic cells. Three primary cultures of melanoma cells, selected for immune phenotype and growth rate, were grafted into BALB/c nu/nu mice that were injected intraperitoneally with different dose- and time-schedules of 5-AZA-CdR. Molecular analyses demonstrated a de novo long-lasting expression of the CTA MAGE-1, -2, -3, -4, -10, GAGE 1–6, NY-ESO-1, and the upregulation of MAGE-1, MAGE-3, and NY-ESO-1 levels in melanoma xenografts from 5-AZA-CdR-treated mice. Serological and biochemical analyses identified a de novo expression of NY-ESO-1 protein and a concomitant and persistent upregulation of HLA class I antigens and of HLA-A1 and -A2 alleles. Immunization of BALB/c mice with 5-AZA-CdR-treated melanoma cells generated high titer circulating anti-NY-ESO-1 antibodies. Altogether, the data obtained identify an immunomodulatory activity of 5-AZA-CdR in vivo and strongly suggest for its clinical use to design novel strategies of CTA-based chemo-immunotherapy for melanoma patients. J. Cell. Physiol. 207: 58–66, 2006. © 2005 Wiley-Liss, Inc.
- Subjects
DNA; ANTIGENS; TESTIS; CELLS; LABORATORY mice; HLA histocompatibility antigens
- Publication
Journal of Cellular Physiology, 2006, Vol 207, Issue 1, p58
- ISSN
0021-9541
- Publication type
Article
- DOI
10.1002/jcp.20540