PPARγ induces PD-L1 expression in MSS+ colorectal cancer cells.
Immunotherapy
MSS
PD-L1
PPAR
cancer
colorectal
Journal
Oncoimmunology
ISSN: 2162-402X
Titre abrégé: Oncoimmunology
Pays: United States
ID NLM: 101570526
Informations de publication
Date de publication:
05 05 2021
05 05 2021
Historique:
entrez:
24
5
2021
pubmed:
25
5
2021
medline:
3
8
2021
Statut:
epublish
Résumé
Only a small subset of colorectal cancer (CRC) patients benefits from immunotherapies, comprising blocking antibodies (Abs) against checkpoint receptor "programmed-cell-death-1" (PD1) and its ligand (PD-L1), because most cases lack the required mutational burden and neo-antigen load caused by microsatellite instability (MSI) and/or an inflamed, immune cell-infiltrated PD-L1+ tumor microenvironment. Peroxisome proliferator-activated-receptor-gamma (PPARγ), a metabolic transcription factor stimulated by anti-diabetic drugs, has been previously implicated in pre/clinical responses to immunotherapy. We therefore raised the hypothesis that PPARγ induces PD-L1 on microsatellite stable (MSS) tumor cells to enhance Ab-target engagement and responsiveness to PD-L1 blockage. We found that PPARγ-agonists upregulate PD-L1 mRNA/protein expression in human gastrointestinal cancer cell lines and MSS+ patient-derived tumor organoids (PDOs). Mechanistically, PPARγ bound to and activated DNA-motifs similar to cognate PPARγ-responsive-elements (PPREs) in the proximal -2 kb promoter of the human
Identifiants
pubmed: 34026331
doi: 10.1080/2162402X.2021.1906500
pii: 1906500
pmc: PMC8115557
doi:
Substances chimiques
B7-H1 Antigen
0
PPAR gamma
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1906500Informations de copyright
© 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.
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