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Cancer testis antigens expression in mesothelioma: role of DNA methylation and bioimmunotherapeutic implications

By L Sigalotti, S Coral, M Altomonte, L Natali, G Gaudino, P Cacciotti, R Libener, F Colizzi, G Vianale, F Martini, M Tognon, A Jungbluth, J Cebon, E Maraskovsky, L Mutti and M Maio

Abstract

Recent evidences suggest that malignant mesothelioma may be sensitive to immunotherapy; however, little is known about malignant mesothelioma-associated tumour antigens. Focusing on cancer/testis antigens, the expression of well-characterised immunogenic tumour-associated antigens was investigated in malignant mesothelioma cells. At variance with MAGE-4 and NY-ESO-1, malignant mesothelioma cells frequently expressed MAGE-1, -2 and -3, GAGE 1-2, GAGE 1-6, SSX-2 and SSX 1-5, and distinct malignant mesothelioma cells concomitantly expressed at least four cancer/testis antigens. Additionally, the tumour-associated antigens RAGE-1 was expressed at high levels in both benign and malignant mesothelial cells. Lastly, treatment with the DNA hypomethylating agent 5-aza-2′-deoxycytidine induced and up-regulated the expression of the cancer/testis antigen examined in malignant mesothelioma cells. Overall, these findings strongly suggest that cancer/testis antigens-based immunotherapy may represent a suitable therapeutic approach to malignant mesothelioma, and foresee the clinical use of 5-aza-2′-deoxycytidine to design new chemo-immunotherapeutic strategies in malignant mesothelioma patients

Topics: Experimental Therapeutics
Publisher: Nature Publishing Group
OAI identifier: oai:pubmedcentral.nih.gov:2364149
Provided by: PubMed Central
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