title: Cancer testis antigens expression in mesothelioma: role of DNA methylation and bioimmunotherapeutic implications.
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.
authors.affiliation: Cancer Bioimmunotherapy Unit, Centro di Riferimento Oncologico, IRCCS, 33081 Aviano, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Sigalotti
authors.forename: S
authors.initials: S
authors.lastname: Coral
authors.forename: M
authors.initials: M
authors.lastname: Altomonte
authors.forename: L
authors.initials: L
authors.lastname: Natali
authors.forename: G
authors.initials: G
authors.lastname: Gaudino
authors.forename: P
authors.initials: P
authors.lastname: Cacciotti
authors.forename: R
authors.initials: R
authors.lastname: Libener
authors.forename: F
authors.initials: F
authors.lastname: Colizzi
authors.forename: G
authors.initials: G
authors.lastname: Vianale
authors.forename: F
authors.initials: F
authors.lastname: Martini
authors.forename: M
authors.initials: M
authors.lastname: Tognon
authors.forename: A
authors.initials: A
authors.lastname: Jungbluth
authors.forename: J
authors.initials: J
authors.lastname: Cebon
authors.forename: E
authors.initials: E
authors.lastname: Maraskovsky
authors.forename: L
authors.initials: L
authors.lastname: Mutti
authors.forename: M
authors.initials: M
authors.lastname: Maio
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000032:analysis*; D001374:Azacitidine / Q000494:pharmacology; D019175:DNA Methylation; D005260:Female; D006801:Humans; D007167:Immunotherapy; D008297:Male; D058950:Melanoma-Specific Antigens; D008565:Membrane Proteins; D008654:Mesothelioma / Q000276:immunology* / Q000628:therapy; D009363:Neoplasm Proteins / Q000032:analysis; D011506:Proteins / Q000032:analysis; D011817:Rabbits; D012097:Repressor Proteins / Q000032:analysis; D013737:Testis / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; C095365:GAGE1 protein, human; C072011:MAGEA1 protein, human; D058950:Melanoma-Specific Antigens; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D011506:Proteins; D012097:Repressor Proteins; C093962:synovial sarcoma X breakpoint proteins; D001374:Azacitidine