Reversal of epigenetic silencing of MHC class I chain-related protein A and B improves immune recognition of Merkel cell carcinoma
Please always quote using this URN: urn:nbn:de:bvb:20-opus-167992
- 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 absentMerkel 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.…
Author: | Cathrin Ritter, Kaiji Fan, Kelly G. Paulson, Paul Nghiem, David Schrama, Jürgen C. Becker |
---|---|
URN: | urn:nbn:de:bvb:20-opus-167992 |
Document Type: | Journal article |
Faculties: | Medizinische Fakultät / Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie |
Language: | English |
Parent Title (English): | Scientific Reports |
Year of Completion: | 2016 |
Edition: | 6 |
Issue: | 21678 |
Source: | Scientific Reports 6:21678 (2016). DOI: 10.1038/srep21678 |
DOI: | https://doi.org/10.1038/srep21678 |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Tag: | MHC class I chain-related protein; Merkel cell carcinoma; epigenetic silencing; skin cancer |
Release Date: | 2019/08/29 |
EU-Project number / Contract (GA) number: | 277775 |
OpenAIRE: | OpenAIRE |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |