Research article summary (published 13 Oct 2009):

Quantitative expression and immunogenicity of MAGE-3 and -6 in upper aerodigestive tract cancer.

Full Abstract

The MAGE antigens are frequently expressed cancer vaccine targets. However, quantitative analysis of MAGE expression in upper aerodigestive tract (UADT) tumor cells and its association with T-cell recognition has not been performed, hindering the selection of appropriate candidates for MAGE-specific immunotherapy. Using quantitative RT-PCR (QRT-PCR), we evaluated the expression of MAGE-3/6 in 65 UADT cancers, 48 normal samples from tumor matched sites and 7 HLA-A*0201+ squamous cell carcinoma of the head and neck (SCCHN) cell lines. Expression results were confirmed using Western blot. HLA-A*0201:MAGE-3- (271-279) specific cytotoxic T lymphocytes (MAGE-CTL) from SCCHN patients and healthy donors showed that MAGE-3/6 expression was highly associated with CTL recognition in vitro. On the basis of the MAGE-3/6 expression, we could identify 31 (47%) of the 65 UADT tumors, which appeared to express MAGE-3/6 at levels that correlated with efficient CTL recognition. To confirm that the level of MAGE-3 expression was responsible for CTL recognition, 2 MAGE-3/6 mRNA(high) SCCHN cell lines, PCI-13 and PCI-30, were subjected to MAGE-3/6-specific knockdown. RNAi-transfected cells showed that MAGE expression and MAGE-CTL recognition were significantly reduced. Furthermore, treatment of cells expressing low MAGE-3/6 mRNA with a demethylating agent, 5-aza-2'-deoxycytidine (DAC), increased the expression of MAGE-3/6 and CTL recognition. Thus, using QRT-PCR UADT cancers frequently express MAGE-3/6 at levels sufficient for CTL recognition, supporting the use of a QRT-PCR-based assay for the selection of candidates likely to respond to MAGE-3/6 immunotherapy. Demethylating agents could increase the number of patients amenable for targeting epigenetically modified tumor antigens in vaccine trials.

Author information

Author/s: Filho, Pedro A Andrade (PA); López-Albaitero, Andrés (A); Xi, Liqiang (L); Gooding, William (W); Godfrey, Tony (T); Ferris, Robert L (RL);

Affiliation: Department of Otolaryngology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.

Grants: R01 CA111806 (Agency:NCI NIH HHS)

Journal and publication information

Publication Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural

Journal: International journal of cancer. Journal international du cancer (Int J Cancer), published in United States. (Language: eng)

Reference: 2009-Oct; vol 125 (issue 8) : pp 1912-20

Dates: Created 2009/08/26; Completed 2009/09/21; Revised 2009/10/06;

PMID: 19610063, status: MEDLINE (last retrieval date: 10/7/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Antigens, Neoplasm - metabolism Blotting, Western Carcinoma, Squamous Cell - metabolism; pathology Case-Control Studies Cytotoxicity, Immunologic DNA Methylation Esophageal Neoplasms - metabolism; pathology Flow Cytometry Gene Expression Regulation, Neoplastic Head and Neck Neoplasms - metabolism; pathology Humans

Humans Immunoenzyme Techniques Interferon-gamma - metabolism Lung Neoplasms - metabolism; pathology Neoplasm Proteins - metabolism Peptide Fragments - metabolism Prognosis RNA, Messenger - genetics; metabolism RNA, Small Interfering - pharmacology Reverse Transcriptase Polymerase Chain Reaction T-Lymphocytes, Cytotoxic - immunology; pathology

Associated Chemicals: Antigens, Neoplasm (0) ; MAGEA3 protein, human (0) ; MAGEA6 protein, human (0) ; Neoplasm Proteins (0) ; Peptide Fragments (0) ; RNA, Messenger (0) ; RNA, Small Interfering (0) ; Interferon-gamma (82115-62-6)

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