Histone deacetylase inhibitors induce TAP, LMP, Tapasin genes and MHC class I antigen presentation by melanoma cells.
Histone deacetylase inhibitors (HDACi), including trichostatin A (TSA) and valproic acid, can alter the acetylation of histones in chromatin and enhance gene transcription. Previously we demonstrated that HDACi-treated tumor cells are capable of presenting antigen via the MHC class II pathway. In this study, we show that treatment with HDACi enhances the expression of molecules (TAP1, TAP2, LMP2, LMP7, Tapasin and MHC class I) involved in antigen processing and presentation via the MHC class I pathway in melanoma cells. HDACi treatment of B16F10 cells also enhanced cell surface expression of class I and costimulatory molecules CD40 and CD86. Enhanced transcription of these genes is associated with a significant increase in direct presentation of whole protein antigen and MHC class I-restricted peptides by TSA-treated B16F10 cells. Our data indicate that epigenetic modification can convert a tumor cell to an antigen presenting cell capable of activating IFN-gamma secreting T cells via the class I pathway. These findings suggest that the abnormalities, observed in some tumors in the expression of MHC class I antigen processing and presentation molecules, may result from epigenetic repression.
Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
A Nazmul H
AN
Khan
Christopher J
CJ
Gregorie
Thomas B
TB
Tomasi
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D000818:Animals; D017951:Antigen Presentation / Q000502:physiology*; D045744:Cell Line, Tumor; D003546:Cysteine Endopeptidases / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D044127:Epigenesis, Genetic; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000187:drug effects / Q000276:immunology; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids / Q000494:pharmacology*; D008545:Melanoma / Q000235:genetics / Q000276:immunology*; D026901:Membrane Transport Proteins / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D051379:Mice; D009097:Multienzyme Complexes / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D046988:Proteasome Endopeptidase Complex; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014635:Valproic Acid / Q000494:pharmacology*
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D004791:Enzyme Inhibitors; D015395:Histocompatibility Antigens Class I; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D026901:Membrane Transport Proteins; D009097:Multienzyme Complexes; C486171:Tap1 protein, mouse; C489516:Tap2 protein, mouse; C107762:tapasin; C071313:LMP-2 protein; C012589:trichostatin A; D014635:Valproic Acid; D003546:Cysteine Endopeptidases; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex