Matches in SemOpenAlex for { <https://semopenalex.org/work/W4313408086> ?p ?o ?g. }
Showing items 1 to 66 of
66
with 100 items per page.
- W4313408086 endingPage "176.15" @default.
- W4313408086 startingPage "176.15" @default.
- W4313408086 abstract "Abstract Poly(ADP-ribose) polymerase (PARP) inhibitors have been a remarkable breakthrough in the treatment of ovarian cancers with BRCA1/2 mutations. We have previously reported that PARP-inhibition with immune checkpoint blockade extended survival of BRCA1-deficient ovarian cancer (ov ca) preclinical models. A significant increase in IFNg producing effector T cells in the tumor environment promoted tumor cytotoxicity in a caspase-independent manner. In this study, we hypothesized that in the presence of IFNg, PARPi may induce immunogenic cell death (ICD) rather than apoptosis and promote immune-mediated tumor control. In vitro, PARPi+IFNg treatment induces hallmarks of ICD in BRCAmt ov ca; such as cell surface translocation of calreticulin, ATP and HMGB-1 release but not by PARPi or IFNg single treatment. Additionally, the PARPi+IFNg treated Ov ca cells induced maturation and activation of dendritic cells with enhanced antigen-presentation to stimulate anti-tumor T cells. Evidence of immunogenicity was confirmed by the benefit of vaccination with PARPi+IFNg treated Ov ca cells in vivo. The vaccination established the long-lasting protective anti-tumor immune responses to clear sequential tumor inoculations. T cell-depletion and adoptive transfer experiments showed the ICD-induced tumor immunity was surprisingly, both CD4 and CD8 T cell-mediated. Currently, we are addressing whether anti-tumor antibodies contribute to tumor control. Our results identified a novel mechanism by which PARP-inhibition with IFNg induces ICD in the ovarian tumor environment. These effects can be leveraged to enhance tumor clearance in the combination with immune therapies to modulate TME by stimulating tumor-immune cycles. Supported by grants from NCI (R37 CA229221)" @default.
- W4313408086 created "2023-01-06" @default.
- W4313408086 creator A5044231660 @default.
- W4313408086 creator A5076933014 @default.
- W4313408086 date "2022-05-01" @default.
- W4313408086 modified "2023-09-25" @default.
- W4313408086 title "PARP-inhibition with IFNg in the ovarian tumor microenvironment induces immunogenic cancer cell death for sustained anti-tumor immunity." @default.
- W4313408086 doi "https://doi.org/10.4049/jimmunol.208.supp.176.15" @default.
- W4313408086 hasPublicationYear "2022" @default.
- W4313408086 type Work @default.
- W4313408086 citedByCount "0" @default.
- W4313408086 crossrefType "journal-article" @default.
- W4313408086 hasAuthorship W4313408086A5044231660 @default.
- W4313408086 hasAuthorship W4313408086A5076933014 @default.
- W4313408086 hasConcept C121608353 @default.
- W4313408086 hasConcept C126322002 @default.
- W4313408086 hasConcept C167672396 @default.
- W4313408086 hasConcept C203014093 @default.
- W4313408086 hasConcept C2776090121 @default.
- W4313408086 hasConcept C2776107976 @default.
- W4313408086 hasConcept C2777701055 @default.
- W4313408086 hasConcept C2777877232 @default.
- W4313408086 hasConcept C2780084626 @default.
- W4313408086 hasConcept C2780427987 @default.
- W4313408086 hasConcept C2780868878 @default.
- W4313408086 hasConcept C502942594 @default.
- W4313408086 hasConcept C71924100 @default.
- W4313408086 hasConcept C86803240 @default.
- W4313408086 hasConcept C8891405 @default.
- W4313408086 hasConcept C90375314 @default.
- W4313408086 hasConceptScore W4313408086C121608353 @default.
- W4313408086 hasConceptScore W4313408086C126322002 @default.
- W4313408086 hasConceptScore W4313408086C167672396 @default.
- W4313408086 hasConceptScore W4313408086C203014093 @default.
- W4313408086 hasConceptScore W4313408086C2776090121 @default.
- W4313408086 hasConceptScore W4313408086C2776107976 @default.
- W4313408086 hasConceptScore W4313408086C2777701055 @default.
- W4313408086 hasConceptScore W4313408086C2777877232 @default.
- W4313408086 hasConceptScore W4313408086C2780084626 @default.
- W4313408086 hasConceptScore W4313408086C2780427987 @default.
- W4313408086 hasConceptScore W4313408086C2780868878 @default.
- W4313408086 hasConceptScore W4313408086C502942594 @default.
- W4313408086 hasConceptScore W4313408086C71924100 @default.
- W4313408086 hasConceptScore W4313408086C86803240 @default.
- W4313408086 hasConceptScore W4313408086C8891405 @default.
- W4313408086 hasConceptScore W4313408086C90375314 @default.
- W4313408086 hasIssue "1_Supplement" @default.
- W4313408086 hasLocation W43134080861 @default.
- W4313408086 hasOpenAccess W4313408086 @default.
- W4313408086 hasPrimaryLocation W43134080861 @default.
- W4313408086 hasRelatedWork W2322919275 @default.
- W4313408086 hasRelatedWork W2741403108 @default.
- W4313408086 hasRelatedWork W2755809284 @default.
- W4313408086 hasRelatedWork W2904909612 @default.
- W4313408086 hasRelatedWork W3096600782 @default.
- W4313408086 hasRelatedWork W4291378227 @default.
- W4313408086 hasRelatedWork W4313385250 @default.
- W4313408086 hasRelatedWork W4327715451 @default.
- W4313408086 hasRelatedWork W4360868614 @default.
- W4313408086 hasRelatedWork W4366590730 @default.
- W4313408086 hasVolume "208" @default.
- W4313408086 isParatext "false" @default.
- W4313408086 isRetracted "false" @default.
- W4313408086 workType "article" @default.