Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Ritter, C; Fan, K; Paulson, KG; Nghiem, P; Schrama, D; Becker, JC.
Reversal of epigenetic silencing of MHC class I chain-related protein A and B improves immune recognition of Merkel cell carcinoma.
Sci Rep. 2016; 6:21678-21678
Doi: 10.1038/srep21678
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Web of Science
PubMed
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- Leading authors Med Uni Graz
- Becker Jürgen Christian
- Ritter Cathrin
- Co-authors Med Uni Graz
- Fan Kaiji
- Schrama David
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- Abstract:
- Merkel cell carcinoma (MCC) is a virally associated cancer characterized by its aggressive behavior and strong immunogenicity. Both viral infection and malignant transformation induce expression of MHC class I chain-related protein (MIC) A and B, which signal stress to cells of the immune system via Natural Killer group 2D (NKG2D) resulting in elimination of target cells. However, despite transformation and the continued presence of virally-encoded proteins, MICs are only expressed in a minority of MCC tumors in situ and are completely absent on MCC cell lines in vitro. This lack of MIC expression was due to epigenetic silencing via MIC promoter hypo-acetylation; indeed, MIC expression was re-induced by pharmacological inhibition of histone deacetylases (HDACs) both in vitro and in vivo. This re-induction of MICs rendered MCC cells more sensitive to immune-mediated lysis. Thus, epigenetic silencing of MICs is an important immune escape mechanism of MCCs.
- Find related publications in this database (using NLM MeSH Indexing)
- Acetylation - drug effects
- Animals -
- Carcinoma, Merkel Cell - drug therapy
- Carcinoma, Merkel Cell - genetics
- Carcinoma, Merkel Cell - immunology
- Carcinoma, Merkel Cell - pathology
- Cell Line, Tumor -
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- Gene Silencing - drug effects
- Gene Silencing - immunology
- Histocompatibility Antigens Class I - genetics
- Histocompatibility Antigens Class I - immunology
- Histone Deacetylase Inhibitors - pharmacology
- Histone Deacetylases - genetics
- Histone Deacetylases - immunology
- Histones - genetics
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- Killer Cells, Lymphokine-Activated - immunology
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- NK Cell Lectin-Like Receptor Subfamily K - genetics
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- Plicamycin - pharmacology
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