Methylation-regulated expression of cancer testis antigens in primary effusion lymphoma: immunotherapeutic implications

J Cell Physiol. 2005 Feb;202(2):474-7. doi: 10.1002/jcp.20133.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism*
  • Azacitidine / analogs & derivatives*
  • Azacitidine / pharmacology
  • Blotting, Western
  • Cell Line, Tumor
  • DNA Methylation*
  • Decitabine
  • Humans
  • Immunoprecipitation
  • Immunotherapy
  • Lymphoma, B-Cell / genetics*
  • Lymphoma, B-Cell / immunology
  • Lymphoma, B-Cell / metabolism*
  • Lymphoma, B-Cell / therapy
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Up-Regulation

Substances

  • Antigens, Neoplasm
  • RNA, Messenger
  • Decitabine
  • Azacitidine