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Histone deacetylase inhibitors induce TAP, LMP, Tapasin genes and MHC class I antigen presentation by melanoma cells

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Abstract

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-γ 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.

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Abbreviations

CTL:

Cytotoxic T lymphocyte

HDACi:

Histone deacetylase inhibitors

TSA:

Trichostatin A

VA:

Valproic acid

APC:

Antigen presenting cell

ova:

Ovalbumin

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Acknowledgments

Supported by a National Institutes of Health grant HD 17013 and utilized core facilities of Roswell Park Cancer Institute’s NCI Cancer Center Support Grant CA16056.

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Correspondence to Thomas B. Tomasi.

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Khan, A.N.H., Gregorie, C.J. & Tomasi, T.B. Histone deacetylase inhibitors induce TAP, LMP, Tapasin genes and MHC class I antigen presentation by melanoma cells. Cancer Immunol Immunother 57, 647–654 (2008). https://doi.org/10.1007/s00262-007-0402-4

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  • DOI: https://doi.org/10.1007/s00262-007-0402-4

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