Methylation-regulated expression of cancer testis antigens in primary effusion lymphoma: immunotherapeutic implications.
Primary effusion lymphoma (PEL) is a large B-cell neoplasm with an unfavorable prognosis and limited therapeutic options. In this study, cancer testis antigens (CTA) were investigated as potential immunotherapeutic targets in patients with PEL. Baseline expression of a panel of 11 CTA was highly heterogeneous among five PEL cell lines. In particular, the investigated CTA were not expressed in BC-2 and BC-3 cells, while BC-1, HBL-6, and BCBL-1 cells tested positive for 6, 8, and 9 CTA, respectively. The DNA hypomethylating agent 5-aza-2'-deoxycytdine (5-AZA-CdR) invariably induced or up-regulated the expression of all investigated CTA in all cell lines analyzed. The de novo expression of CTA was still detectable at mRNA and protein level at least 2 months after the end of 5-AZA-CdR treatment. These findings, and the concomitant up-regulation of HLA-class I antigens and ICAM-1 by 5-AZA-CdR, support its clinical use to set-up innovative chemo-immunotherapeutic approaches in PEL.
Calabrò
Luana
L
Cancer Bioimmunotherapy Unit, Department of Medical Oncology, Centro di Riferimento Oncologico, IRCCS, Aviano, Italy.
Fonsatti
Ester
E
Altomonte
Maresa
M
Pezzani
Laura
L
Colizzi
Francesca
F
Nanni
Paola
P
Gattei
Valter
V
Sigalotti
Luca
L
Maio
Michele
M
D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D019175:DNA Methylation; D000077209:Decitabine; D006801:Humans; D047468:Immunoprecipitation; D007167:Immunotherapy; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000276:immunology / Q000378:metabolism* / Q000628:therapy; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D015854:Up-Regulation
D000951:Antigens, Neoplasm; D012333:RNA, Messenger; D000077209:Decitabine; D001374:Azacitidine