Immunoproteasome expression is associated with better prognosis and response to checkpoint therapies in melanoma.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
14 02 2020
14 02 2020
Historique:
received:
10
10
2018
accepted:
16
01
2020
entrez:
16
2
2020
pubmed:
16
2
2020
medline:
2
6
2020
Statut:
epublish
Résumé
Predicting the outcome of immunotherapy treatment in melanoma patients is challenging. Alterations in genes involved in antigen presentation and the interferon gamma (IFNγ) pathway play an important role in the immune response to tumors. We describe here that the overexpression of PSMB8 and PSMB9, two major components of the immunoproteasome, is predictive of better survival and improved response to immune-checkpoint inhibitors of melanoma patients. We study the mechanism underlying this connection by analyzing the antigenic peptide repertoire of cells that overexpress these subunits using HLA peptidomics. We find a higher response of patient-matched tumor infiltrating lymphocytes against antigens diferentially presented after immunoproteasome overexpression. Importantly, we find that PSMB8 and PSMB9 expression levels are much stronger predictors of melanoma patients' immune response to checkpoint inhibitors than the tumors' mutational burden. These results suggest that PSMB8 and PSMB9 expression levels can serve as important biomarkers for stratifying melanoma patients for immune-checkpoint treatment.
Identifiants
pubmed: 32060274
doi: 10.1038/s41467-020-14639-9
pii: 10.1038/s41467-020-14639-9
pmc: PMC7021791
doi:
Substances chimiques
LMP-2 protein
144416-78-4
Interferon-gamma
82115-62-6
Cysteine Endopeptidases
EC 3.4.22.-
LMP7 protein
EC 3.4.25.1
Proteasome Endopeptidase Complex
EC 3.4.25.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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