Cancer testis antigens expression in mesothelioma: role of DNA methylation and bioimmunotherapeutic implications.
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.
Sigalotti
L
L
Cancer Bioimmunotherapy Unit, Centro di Riferimento Oncologico, IRCCS, 33081 Aviano, Italy.
Coral
S
S
Altomonte
M
M
Natali
L
L
Gaudino
G
G
Cacciotti
P
P
Libener
R
R
Colizzi
F
F
Vianale
G
G
Martini
F
F
Tognon
M
M
Jungbluth
A
A
Cebon
J
J
Maraskovsky
E
E
Mutti
L
L
Maio
M
M
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*
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