title: Methylation-regulated expression of cancer testis antigens in primary effusion lymphoma: immunotherapeutic implications.
abstract: 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.
authors.affiliation: Cancer Bioimmunotherapy Unit, Department of Medical Oncology, Centro di Riferimento Oncologico, IRCCS, Aviano, Italy.
authors.forename: Luana
authors.initials: L
authors.lastname: Calabrò
authors.forename: Ester
authors.initials: E
authors.lastname: Fonsatti
authors.forename: Maresa
authors.initials: M
authors.lastname: Altomonte
authors.forename: Laura
authors.initials: L
authors.lastname: Pezzani
authors.forename: Francesca
authors.initials: F
authors.lastname: Colizzi
authors.forename: Paola
authors.initials: P
authors.lastname: Nanni
authors.forename: Valter
authors.initials: V
authors.lastname: Gattei
authors.forename: Luca
authors.initials: L
authors.lastname: Sigalotti
authors.forename: Michele
authors.initials: M
authors.lastname: Maio
mesh_terms: 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
chemical_list: D000951:Antigens, Neoplasm; D012333:RNA, Messenger; D000077209:Decitabine; D001374:Azacitidine