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dc.contributor.authorHaggerty, Timothy J.en_US
dc.contributor.authorDunn, Ian S.en_US
dc.contributor.authorRose, Lenora B.en_US
dc.contributor.authorNewton, Estelle E.en_US
dc.contributor.authorPandolfi, Francoen_US
dc.contributor.authorKurnick, James T.en_US
dc.date.accessioned2015-01-05T18:25:56Z
dc.date.issued2014en_US
dc.identifier.citationHaggerty, Timothy J., Ian S. Dunn, Lenora B. Rose, Estelle E. Newton, Franco Pandolfi, and James T. Kurnick. 2014. “Heat Shock Protein-90 Inhibitors Enhance Antigen Expression on Melanomas and Increase T Cell Recognition of Tumor Cells.” PLoS ONE 9 (12): e114506. doi:10.1371/journal.pone.0114506. http://dx.doi.org/10.1371/journal.pone.0114506.en
dc.identifier.issn1932-6203en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:13581013
dc.description.abstractIn an effort to enhance antigen-specific T cell recognition of cancer cells, we have examined numerous modulators of antigen-expression. In this report we demonstrate that twelve different Hsp90 inhibitors (iHsp90) share the ability to increase the expression of differentiation antigens and MHC Class I antigens. These iHsp90 are active in several molecular and cellular assays on a series of tumor cell lines, including eleven human melanomas, a murine B16 melanoma, and two human glioma-derived cell lines. Intra-cytoplasmic antibody staining showed that all of the tested iHsp90 increased expression of the melanocyte differentiation antigens Melan-A/MART-1, gp100, and TRP-2, as well as MHC Class I. The gliomas showed enhanced gp100 and MHC staining. Quantitative analysis of mRNA levels showed a parallel increase in message transcription, and a reporter assay shows induction of promoter activity for Melan-A/MART-1 gene. In addition, iHsp90 increased recognition of tumor cells by T cells specific for Melan-A/MART-1. In contrast to direct Hsp90 client proteins, the increased levels of full-length differentiation antigens that result from iHsp90 treatment are most likely the result of transcriptional activation of their encoding genes. In combination, these results suggest that iHsp90 improve recognition of tumor cells by T cells specific for a melanoma-associated antigen as a result of increasing the expressed intracellular antigen pool available for processing and presentation by MHC Class I, along with increased levels of MHC Class I itself. As these Hsp90 inhibitors do not interfere with T cell function, they could have potential for use in immunotherapy of cancer.en
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.relation.isversionofdoi:10.1371/journal.pone.0114506en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4264751/pdf/en
dash.licenseLAAen_US
dc.subjectBiology and Life Sciencesen
dc.subjectCell Biologyen
dc.subjectCellular Typesen
dc.subjectAnimal Cellsen
dc.subjectBlood Cellsen
dc.subjectWhite Blood Cellsen
dc.subjectT Cellsen
dc.subjectTumor-Infiltrating Lymphocytesen
dc.subjectImmune Cellsen
dc.subjectImmunologyen
dc.subjectClinical Immunologyen
dc.subjectTumor Immunologyen
dc.subjectAntigen Processing and Recognitionen
dc.subjectMedicine and Health Sciencesen
dc.titleHeat Shock Protein-90 Inhibitors Enhance Antigen Expression on Melanomas and Increase T Cell Recognition of Tumor Cellsen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalPLoS ONEen
dash.depositing.authorKurnick, James T.en_US
dc.date.available2015-01-05T18:25:56Z
dc.identifier.doi10.1371/journal.pone.0114506*
dash.contributor.affiliatedKurnick, James


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