Epigenetic priming restores the HLA class-I antigen processing machinery expression in Merkel cell carcinoma

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 cla...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Cathrin Ritter, Kaiji Fan, Annette Paschen, Sine Reker Hardrup, Soldano Ferrone, Paul Nghiem, Selma Ugurel, David Schrama, Jürgen C. Becker
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8a93f8dccd0d4f538a485c5193e1806a
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:8a93f8dccd0d4f538a485c5193e1806a
record_format	dspace
spelling	oai:doaj.org-article:8a93f8dccd0d4f538a485c5193e1806a2021-12-02T15:06:14ZEpigenetic priming restores the HLA class-I antigen processing machinery expression in Merkel cell carcinoma10.1038/s41598-017-02608-02045-2322https://doaj.org/article/8a93f8dccd0d4f538a485c5193e1806a2017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02608-0https://doaj.org/toc/2045-2322Abstract 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.Cathrin RitterKaiji FanAnnette PaschenSine Reker HardrupSoldano FerronePaul NghiemSelma UgurelDavid SchramaJürgen C. BeckerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Cathrin Ritter Kaiji Fan Annette Paschen Sine Reker Hardrup Soldano Ferrone Paul Nghiem Selma Ugurel David Schrama Jürgen C. Becker Epigenetic priming restores the HLA class-I antigen processing machinery expression in Merkel cell carcinoma
description	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.
format	article
author	Cathrin Ritter Kaiji Fan Annette Paschen Sine Reker Hardrup Soldano Ferrone Paul Nghiem Selma Ugurel David Schrama Jürgen C. Becker
author_facet	Cathrin Ritter Kaiji Fan Annette Paschen Sine Reker Hardrup Soldano Ferrone Paul Nghiem Selma Ugurel David Schrama Jürgen C. Becker
author_sort	Cathrin Ritter
title	Epigenetic priming restores the HLA class-I antigen processing machinery expression in Merkel cell carcinoma
title_short	Epigenetic priming restores the HLA class-I antigen processing machinery expression in Merkel cell carcinoma
title_full	Epigenetic priming restores the HLA class-I antigen processing machinery expression in Merkel cell carcinoma
title_fullStr	Epigenetic priming restores the HLA class-I antigen processing machinery expression in Merkel cell carcinoma
title_full_unstemmed	Epigenetic priming restores the HLA class-I antigen processing machinery expression in Merkel cell carcinoma
title_sort	epigenetic priming restores the hla class-i antigen processing machinery expression in merkel cell carcinoma
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/8a93f8dccd0d4f538a485c5193e1806a
work_keys_str_mv	AT cathrinritter epigeneticprimingrestoresthehlaclassiantigenprocessingmachineryexpressioninmerkelcellcarcinoma AT kaijifan epigeneticprimingrestoresthehlaclassiantigenprocessingmachineryexpressioninmerkelcellcarcinoma AT annettepaschen epigeneticprimingrestoresthehlaclassiantigenprocessingmachineryexpressioninmerkelcellcarcinoma AT sinerekerhardrup epigeneticprimingrestoresthehlaclassiantigenprocessingmachineryexpressioninmerkelcellcarcinoma AT soldanoferrone epigeneticprimingrestoresthehlaclassiantigenprocessingmachineryexpressioninmerkelcellcarcinoma AT paulnghiem epigeneticprimingrestoresthehlaclassiantigenprocessingmachineryexpressioninmerkelcellcarcinoma AT selmaugurel epigeneticprimingrestoresthehlaclassiantigenprocessingmachineryexpressioninmerkelcellcarcinoma AT davidschrama epigeneticprimingrestoresthehlaclassiantigenprocessingmachineryexpressioninmerkelcellcarcinoma AT jurgencbecker epigeneticprimingrestoresthehlaclassiantigenprocessingmachineryexpressioninmerkelcellcarcinoma
_version_	1718388526657044480

Epigenetic priming restores the HLA class-I antigen processing machinery expression in Merkel cell carcinoma

Ejemplares similares