Histone deacetylase inhibitors induce TAP, LMP, Tapasin genes and MHC class I antigen presentation by melanoma cells
Histone deacetylase inhibitors induce TAP, LMP, Tapasin genes and MHC class I antigen presentation by melanoma cells
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DOI：
10.1007/s00262-007-0402-4
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发表时间：
2008-05-01
影响因子：
5.8
通讯作者：
Tomasi, Thomas B.
中科院分区：
文献类型：
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作者：
Khan, A. Nazmul H.;Gregorie, Christopher J.;Tomasi, Thomas B.
组蛋白去乙酰化酶抑制剂（HDACi），包括曲古霉素A （TSA）和丙戊酸，可以改变染色质中组蛋白的乙酰化并增强基因转录。先前我们证明了hdac处理的肿瘤细胞能够通过MHC II类途径递呈抗原。在这项研究中，我们发现HDACi治疗增强了黑色素瘤细胞中参与抗原加工和递呈的分子（TAP1、TAP2、LMP2、LMP7、Tapasin和MHC I类）的表达，这些分子通过MHC I类途径参与抗原加工和递呈。HDACi处理B16F10细胞也增强了I类和共刺激分子CD40和CD86的细胞表面表达。这些基因转录的增强与tsa处理的B16F10细胞直接呈递全蛋白抗原和MHC i类限制性肽的显著增加有关。我们的数据表明，表观遗传修饰可以将肿瘤细胞转化为抗原提呈细胞，能够通过I类途径激活分泌ifn - γ的T细胞。这些发现表明，在一些肿瘤中观察到的MHC I类抗原加工和递呈分子表达的异常可能是由表观遗传抑制引起的。
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.