Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Ritter, C; Fan, K; Paschen, A; Reker Hardrup, S; Ferrone, S; Nghiem, P; Ugurel, S; Schrama, D; Becker, JC.
Epigenetic priming restores the HLA class-I antigen processing machinery expression in Merkel cell carcinoma.
Sci Rep. 2017; 7(1):2290-2290
Doi: 10.1038/s41598-017-02608-0
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- Führende Autor*innen der Med Uni Graz
- Becker Jürgen Christian
- Ritter Cathrin
- Co-Autor*innen der Med Uni Graz
- Fan Kaiji
- Schrama David
- Ugurel-Becker Selma
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- Abstract:
- Merkel cell carcinoma (MCC) is a rare and aggressive, yet highly immunogenic skin cancer. The latter is due to its viral or UV-associated carcinogenesis. For tumor progression MCC has to escape the host's immuno-surveillance, e.g. by loss of HLA class-I expression. Indeed, a reduced HLA class-I expression was observed in MCC tumor tissues and MCC cell lines. This reduced HLA class-I surface expression is caused by an impaired expression of key components of the antigen processing machinery (APM), including LMP2 and LMP7 as well as TAP1 and TAP2. Notably, experimental provisions of HLA class-I binding peptides restored HLA class-I surface expression on MCC cells. Silencing of the HLA class-I APM is due to histone deacetylation as inhibition of histone deacetylases (HDACs) not only induced acetylation of histones in the respective promoter regions but also re-expression of APM components. Thus, HDAC inhibition restored HLA class-I surface expression in vitro and in a mouse xenotransplantation model. In contrast to re-induction of HLA class-I by interferons, HDAC inhibitors did not interfere with the expression of immuno-dominant viral proteins. In summary, restoration of HLA class-I expression on MCC cells by epigenetic priming is an attractive approach to enhance therapies boosting adaptive immune responses.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Antigen Presentation - genetics
- Antigen Presentation - immunology
- Carcinoma, Merkel Cell - genetics
- Carcinoma, Merkel Cell - immunology
- Carcinoma, Merkel Cell - metabolism
- Cell Line, Tumor -
- Epigenesis, Genetic - genetics
- Epigenesis, Genetic - immunology
- Female -
- Gene Expression Regulation, Neoplastic - immunology
- Histocompatibility Antigens Class I - genetics
- Histocompatibility Antigens Class I - immunology
- Histocompatibility Antigens Class I - metabolism
- Humans -
- Immunohistochemistry -
- Mice, Inbred NOD -
- Mice, SCID -
- Reverse Transcriptase Polymerase Chain Reaction -
- Skin Neoplasms - genetics
- Skin Neoplasms - immunology
- Skin Neoplasms - metabolism
- Transplantation, Heterologous -