Cancer testis antigens expression in mesothelioma: role of DNA methylation and bioimmunotherapeutic implications

Br J Cancer. 2002 Mar 18;86(6):979-82. doi: 10.1038/sj.bjc.6600174.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Neoplasm / analysis*
  • Azacitidine / pharmacology
  • DNA Methylation*
  • Female
  • Humans
  • Immunotherapy
  • Male
  • Melanoma-Specific Antigens
  • Membrane Proteins*
  • Mesothelioma / immunology*
  • Mesothelioma / therapy
  • Neoplasm Proteins / analysis
  • Proteins / analysis
  • Rabbits
  • Repressor Proteins / analysis
  • Testis / immunology*

Substances

  • Antigens, Neoplasm
  • CTAG1B protein, human
  • GAGE1 protein, human
  • MAGEA1 protein, human
  • Melanoma-Specific Antigens
  • Membrane Proteins
  • Neoplasm Proteins
  • Proteins
  • Repressor Proteins
  • synovial sarcoma X breakpoint proteins
  • Azacitidine