Epigenetically regulated clonal heritability of CTA expression profiles in human melanoma

Journal of Cellular Physiology
Elisabetta FrattaMichele Maio

Abstract

The intratumoral heterogeneity of cancer testis antigens (CTA) expression, which is driven by promoter methylation status, may hamper the effectiveness of CTA-directed vaccination of melanoma patients. Thus, we investigated whether the intratumoral heterogeneity of CTA expression is inherited at cellular level, or evolves throughout cellular replication, leading to a phenotypically unstable tumor cell population with reduced immunogenicity and/or able to escape immune control. Utilizing a previously characterized ex vivo clonal model of intratumoral heterogeneity of CTA expression in melanoma, Mel 313 MAGE-A3-low clone 5 (clone 5(M3-low)) and MAGE-A3-high clone 14 (clone 14(M3-high)) were sub-cloned and analyzed for CTA profile. Molecular assays demonstrated that levels of MAGE-A3 expression were highly conserved among generated sub-clones, as compared to parental clones. A similar behavior was identified for an extensive panel of other CTA investigated. Inherited levels of MAGE-A3 expression correlated with the extent of promoter methylation among clone 5(M3-low) and clone 14(M3-high) sub-clones analyzed. Treatment of clone 5(M3-low) with a DNA hypomethylating agent (DHA) resulted in an up-regulated expression of MAGE-A3, whic...Continue Reading

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Citations

Apr 12, 2011·Cancer Immunology, Immunotherapy : CII·Yeranddy A AlpizarN Avrion Mitchison
Nov 10, 2012·Cancer Immunology, Immunotherapy : CII·Sandra CoralMichele Maio
Sep 7, 2012·Journal of Translational Medicine·Luca SigalottiMichele Maio
Jun 15, 2010·Journal of Translational Medicine·Luca SigalottiMichele Maio
Jan 5, 2014·Pharmacology & Therapeutics·Luca SigalottiMichele Maio
Jan 13, 2012·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Beatrix CucuruzBernhard Polzer
Jun 2, 2014·Hematology/oncology Clinics of North America·Kim Margolin
May 13, 2015·Seminars in Oncology·Alessia CovreMichele Maio
Oct 11, 2016·PLoS Genetics·Maximilian StahlThomas Prebet
Nov 23, 2012·Annals of Oncology : Official Journal of the European Society for Medical Oncology·H A TawbiJ M Kirkwood
May 1, 2020·Cytometry. Part B, Clinical Cytometry·Elena MaryamchikMarcela V Maus

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