Cell-autonomous inflammation of BRCA1-deficient ovarian cancers drives both tumor-intrinsic immunoreactivity and immune resistance via STING.

Animals BRCA1 Protein / deficiency Cell Line, Tumor Chemokine CCL5 / metabolism Chromatin / metabolism DNA / metabolism DNA Damage Epigenesis, Genetic Female Gene Silencing Humans Immune Checkpoint Inhibitors / pharmacology Inflammation / complications Interferons / metabolism Membrane Proteins / metabolism Mice, Inbred C57BL Neoplasm Grading Neovascularization, Pathologic / pathology Ovarian Neoplasms / complications Protein Serine-Threonine Kinases / metabolism T-Lymphocytes / immunology Transcription, Genetic Vascular Endothelial Growth Factor A / metabolism

BRCA1 CTLA-4 DNA sensing ICB PARPi PD-L1 STING T cells VEGF-A angiogenesis dual immune checkpoint blockade ovarian cancer type I IFN

Journal

Cell reports

ISSN: 2211-1247

Titre abrégé: Cell Rep

Pays: United States

ID NLM: 101573691

Informations de publication

Date de publication:
20 07 2021

Historique:

received: 28 05 2020

revised: 18 09 2020

accepted: 25 06 2021

entrez: 21 7 2021

pubmed: 22 7 2021

medline: 9 2 2022

Statut: ppublish

Résumé

In this study, we investigate mechanisms leading to inflammation and immunoreactivity in ovarian tumors with homologous recombination deficiency (HRD). BRCA1 loss is found to lead to transcriptional reprogramming in tumor cells and cell-intrinsic inflammation involving type I interferon (IFN) and stimulator of IFN genes (STING). BRCA1-mutated (BRCA1

Identifiants

DOI: 10.1016/j.celrep.2021.109412 PMID: 34289354 PMC: PMC8371260

pubmed: 34289354

pii: S2211-1247(21)00825-1

doi: 10.1016/j.celrep.2021.109412

pmc: PMC8371260

mid: NIHMS1727190

pii:

doi:

Substances chimiques

BRCA1 Protein 0

BRCA1 protein, human 0

Chemokine CCL5 0

Chromatin 0

Immune Checkpoint Inhibitors 0

Membrane Proteins 0

STING1 protein, human 0

Vascular Endothelial Growth Factor A 0

DNA 9007-49-2

Interferons 9008-11-1

Protein Serine-Threonine Kinases EC 2.7.11.1

TBK1 protein, human EC 2.7.11.1

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

109412

Subventions

Organisme : NCI NIH HHS

ID : P50 CA083638

Pays : United States

Informations de copyright

Déclaration de conflit d'intérêts

Declaration of interests G. Coukos has received grants from Celgene, Boehringer-Ingelheim, Roche, BMS, Iovance Therapeutics, and Kite Pharma. The institution G. Coukos is affiliated with has received fees for G. Coukos’ participation on an advisory board or for presentation at a company-sponsored symposium from Genentech, Roche, BMS, AstraZeneca, NextCure, Geneos Tx, and Sanofi/Avensis. G. Coukos has patents in the domain of antibodies and vaccines targeting the tumor vasculature as well as technologies related to T cell expansion and engineering for T cell therapy. G. Coukos holds patents around antibodies and receives royalties from the University of Pennsylvania regarding technology licensed to Novartis. The remaining authors declare no competing interests.

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