title: Human Leukocyte Antigen (HLA) Peptides Derived from Tumor Antigens Induced by Inhibition of DNA Methylation for Development of Drug-facilitated Immunotherapy.
abstract: Treatment of cancer cells with anticancer drugs often fails to achieve complete remission. Yet, such drug treatments may induce alteration in the tumor's gene expression patterns, including those of Cancer/Testis Antigens (CTA). The degradation products of such antigens can be presented as HLA peptides on the surface of the tumor cells and be developed into anticancer immunotherapeutics. For example, the DNA methyl transferase inhibitor, 5-aza-2'-deoxycytidine (Decitabine) has limited antitumor efficacy, yet it induces the expression of many genes, including CTAs that are normally silenced in the healthy adult tissues. In this study, the presentation of many new HLA peptides derived from CTAs and induced by Decitabine was demonstrated in three human Glioblastoma cell lines. Such presentation of CTA-derived HLA peptides can be exploited for development of new treatment modalities, combining drug treatment with anti-CTA targeted immunotherapy. The Decitabine-induced HLA peptidomes include many CTAs that are not normally detected in healthy tissues or in cancer cells, unless treated with the drug. In addition, the study included large-scale analyses of the simultaneous effects of Decitabine on the transcriptomes, proteomes and HLA peptidomes of the human Glioblastoma cells. It demonstrates the poor correlations between these three levels of gene expression, both in their total levels and in their response to the drug. The proteomics and HLA peptidomics data are available via ProteomeXchange with identifier PXD003790 and the transcriptomics data are available via GEO with identifier GSE80137.
authors.affiliation: From the ‡Department of Biology, Technion, Israel Institute of Technology, Haifa, Israel.
authors.forename: Bracha
authors.initials: B
authors.lastname: Shraibman
authors.affiliation: From the ‡Department of Biology, Technion, Israel Institute of Technology, Haifa, Israel.
authors.forename: Dganit Melamed
authors.initials: DM
authors.lastname: Kadosh
authors.affiliation: From the ‡Department of Biology, Technion, Israel Institute of Technology, Haifa, Israel.
authors.forename: Eilon
authors.initials: E
authors.lastname: Barnea
authors.affiliation: From the ‡Department of Biology, Technion, Israel Institute of Technology, Haifa, Israel admon@tx.technion.ac.il.
authors.forename: Arie
authors.identifier: 0000-0003-0504-3950
authors.initials: A
authors.lastname: Admon
mesh_terms: D000951:Antigens, Neoplasm / Q000737:chemistry*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001932:Brain Neoplasms / Q000188:drug therapy / Q000276:immunology*; D045744:Cell Line, Tumor; D019175:DNA Methylation / Q000187:drug effects; D000077209:Decitabine; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000188:drug therapy / Q000276:immunology*; D006680:HLA Antigens / Q000737:chemistry*; D006801:Humans; D007167:Immunotherapy; D010455:Peptides / Q000302:isolation & purification*; D040901:Proteomics / Q000379:methods; D017423:Sequence Analysis, RNA
chemical_list: D000951:Antigens, Neoplasm; D006680:HLA Antigens; D010455:Peptides; D000077209:Decitabine; D001374:Azacitidine