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

Our plain-English summary of Cancer testis antigens expression in mesothelioma: role of DNA methylation and bioimmunotherapeutic implications, by L. Sigalotti, S. Coral, M. Altomonte, et al (British Journal of Cancer, 2002).

The study

• Authors: L. Sigalotti, S. Coral, M. Altomonte, L. Natali, G. Gaudino, P. Cacciotti, R. Libener, F. Colizzi, G. Vianale, F. Martini, M. Tognon, A. Jungbluth, J. Cebon, E. Maraskovsky, L. Mutti, M. Maio
• Journal: British Journal of Cancer
• Published: 2002;86(6):979-82
• Cited by: 78 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

Copyright 2002 Cancer Research UK

In plain English

This laboratory study of cultured cells did not study people or asbestos exposure. The authors tested malignant mesothelioma cells taken from pleural effusions (fluid around the lungs) of mesothelioma patients: three primary cultures and three long-term cultures. Benign mesothelial cells from pleural effusions of heart-failure patients served for comparison. Mainly by detecting RNA, the authors measured whether genes for cancer/testis antigens, which are proteins the immune system can recognise, were active. Five of the six mesothelioma cultures expressed MAGE-1, -2 and/or -3, and each expressed at least four such antigens. MAGE-4 and NY-ESO-1 were found less often. None of these antigens was detected in the benign mesothelial cells. Another antigen, RAGE-1, was found in four of six mesothelioma cultures and also in benign mesothelial cells. Treating mesothelioma cells with the drug 5-aza-2'-deoxycytidine, which reduces DNA methylation, switched on or increased the cancer/testis antigens tested. The one exception was MAGE-3 in one culture. MAGE-3 rose six-fold and 10-fold in two cultures. The authors called the results preliminary and concluded they strongly suggest antigen-based immunotherapy may be a suitable approach to mesothelioma.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) study of cultured cells, using RT-PCR, competitive PCR, immunoprecipitation and Western blotting
• Who was studied: Six malignant mesothelioma cell cultures derived from pleural effusions of mesothelioma patients: three primary cultures (MES-CM98, MES-MM98, MES-OC99) and three long-term cultures (MPP-89, MES-1, MES-2). Benign mesothelial cell cultures came from pleural effusions of patients with heart failure. The number of patients and the place and dates of collection were not stated.
• Exposure: No asbestos exposure was studied. The experimental treatment was the DNA hypomethylating drug 5-aza-2'-deoxycytidine (5-AZA-CdR), applied to mesothelioma cells in the laboratory (for 48 h in the figure experiments).
• Main results:
  • In the six mesothelioma cultures, RT-PCR (an RNA test) showed frequent expression of cancer/testis antigens of the MAGE, GAGE and SSX families. MAGE-4 and NY-ESO-1 were found less often.
  • Five of the six mesothelioma cultures expressed MAGE-1 and/or -2 and/or -3.
  • Each mesothelioma culture expressed at least four cancer/testis antigens at the same time.
  • None of the cancer/testis antigens tested was detected in benign mesothelial cells.
  • The antigen RAGE-1 was expressed by four of six mesothelioma cultures. It was also detected in three primary cultures of benign mesothelial cells.
  • Some mesothelioma cultures lacked one or more of MAGE-1, -2, -3, -4, NY-ESO-1 and SSX-2. In these cultures, 5-AZA-CdR treatment induced expression of the missing cancer/testis antigens. The exception was MAGE-3 in MES-1 cells.
  • Cancer/testis antigens already present in mesothelioma cells gave stronger RT-PCR signals after 5-AZA-CdR treatment. By competitive RT-PCR, MAGE-3 expression rose six-fold in MPP-89 cells and 10-fold in MES-OC99 cells.
  • Protein was tested only for NY-ESO-1, in two cultures. 5-AZA-CdR strongly increased NY-ESO-1 protein in MPP-89 cells and produced new NY-ESO-1 protein in MES-CM98 cells.
  • The authors also reported, without showing data, that 5-AZA-CdR increased HLA class I antigens and two co-stimulatory molecules on MES-MM98 cells.
• The authors' conclusion: The authors concluded that their preliminary results strongly suggest cancer/testis antigen-based immunotherapy may be a suitable treatment approach for malignant mesothelioma. They also said the results provide background for new chemo-immunotherapeutic approaches.
• Limitations the authors state:
  • The authors described their results as preliminary.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Immunotherapy, Mesothelial Cells.

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