dc.contributor.author
Ebstein, Frédéric
dc.contributor.author
Keller, Martin
dc.contributor.author
Paschen, Annette
dc.contributor.author
Walden, Peter
dc.contributor.author
Seeger, Michael
dc.contributor.author
Bürger, Elke
dc.contributor.author
Krüger, Elke
dc.contributor.author
Schadendorf, Dirk
dc.contributor.author
Kloetzel, Peter-M.
dc.contributor.author
Seifert, Ulrike
dc.date.accessioned
2018-06-08T04:02:54Z
dc.date.available
2016-05-30T08:16:22.726Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/16481
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-20662
dc.description.abstract
Efficient processing of target antigens by the ubiquitin-proteasome-system
(UPS) is essential for treatment of cancers by T cell therapies. However,
immune escape due to altered expression of IFN-γ-inducible components of the
antigen presentation machinery and consequent inefficient processing of HLA-
dependent tumor epitopes can be one important reason for failure of such
therapies. Here, we show that short-term co-culture of Melan-A/MART-1 tumor
antigen-expressing melanoma cells with Melan-A/MART-126-35-specific cytotoxic
T lymphocytes (CTL) led to resistance against CTL-induced lysis because of
impaired Melan-A/MART-126-35 epitope processing. Interestingly, deregulation
of p97/VCP expression, which is an IFN-γ-independent component of the UPS and
part of the ER-dependent protein degradation pathway (ERAD), was found to be
essentially involved in the observed immune escape. In support, our data
demonstrate that re-expression of p97/VCP in Melan-A/MART-126-35 CTL-resistant
melanoma cells completely restored immune recognition by Melan-A/MART-126-35
CTL. In conclusion, our experiments show that impaired expression of
IFN-γ-independent components of the UPS can exert rapid immune evasion of
tumor cells and suggest that tumor antigens processed by distinct UPS
degradation pathways should be simultaneously targeted in T cell therapies to
restrict the likelihood of immune evasion due to impaired antigen processing.
en
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::616 Krankheiten
dc.title
Exposure to Melan-A/MART-126-35 tumor epitope specific CD8+T cells reveals
immune escape by affecting the ubiquitin-proteasome system (UPS)
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation
Scientific Reports. - 6 (2016), Artikel Nr. 25208
dcterms.bibliographicCitation.doi
10.1038/srep25208
dcterms.bibliographicCitation.url
http://doi.org/10.1038/srep25208
refubium.affiliation
Charité - Universitätsmedizin Berlin
de
refubium.mycore.fudocsId
FUDOCS_document_000000024627
refubium.note.author
Der Artikel wurde in einer Open-Access-Zeitschrift publiziert.
refubium.resourceType.isindependentpub
no
refubium.mycore.derivateId
FUDOCS_derivate_000000006473
dcterms.accessRights.openaire
open access