Matches in SemOpenAlex for { <https://semopenalex.org/work/W4313382679> ?p ?o ?g. }
Showing items 1 to 74 of
74
with 100 items per page.
- W4313382679 endingPage "162.7" @default.
- W4313382679 startingPage "162.7" @default.
- W4313382679 abstract "Abstract To prime T cells to fight cancer, dendritic cells (DCs) require Type I Interferon (IFN-I) signaling. IFN-I signaling induces the transcription and translation of Interferon Stimulated Genes (ISGs), including strong induction of Usp18, which dampens further IFN-I signaling. We hypothesized that increasing IFN-I signals to DCs in vivo via conditional Usp18 deletion would enhance the ability of DCs to prime T cells, augmenting their anti-tumor activity. To test this, we used Usp18fl/fl x CD11c-cre mice and the syngeneic B16F10 melanoma model. Surprisingly, tumors grew more quickly in Usp18fl/fl x CD11c-cre mice, and intratumoral T cells were less functional post-priming by Usp18-deficient DCs. This functional decrease was coupled with an accelerated effector differentiation marked by early loss of the stem cell-like factor TCF-1. These data suggest that Usp18-deficient DCs expedite terminal effector T cell differentiation, resulting in suppressed effector functionality at later time points. Consistent with this T cell dysfunction, intratumoral STING agonism was less effective at controlling tumors in Usp18fl/fl x CD11c-Cre mice than Usp18fl/fl littermate controls. To understand the molecular drivers of these changes, we profiled DCs with tandem mass tag (TMT) mass spectrometry. We found that Usp18-deficient DCs exhibit deficiencies in mitochondrial function and cysteine biosynthesis, potentially driving their altered ability to prime T cells. Overall, this work highlights the importance of stringent IFN-I signaling regulation for mounting optimal immune responses to cancer. Our findings also identify DC-intrinsic Usp18 expression as a potential biomarker for predicting patient responsiveness to STING agonist therapy." @default.
- W4313382679 created "2023-01-06" @default.
- W4313382679 creator A5010602088 @default.
- W4313382679 creator A5021887509 @default.
- W4313382679 creator A5023203708 @default.
- W4313382679 creator A5043409022 @default.
- W4313382679 creator A5089241426 @default.
- W4313382679 date "2020-05-01" @default.
- W4313382679 modified "2023-09-23" @default.
- W4313382679 title "Too Much of a Good Thing: IFN-I, Dendritic Cells, and Cancer" @default.
- W4313382679 doi "https://doi.org/10.4049/jimmunol.204.supp.162.7" @default.
- W4313382679 hasPublicationYear "2020" @default.
- W4313382679 type Work @default.
- W4313382679 citedByCount "0" @default.
- W4313382679 crossrefType "journal-article" @default.
- W4313382679 hasAuthorship W4313382679A5010602088 @default.
- W4313382679 hasAuthorship W4313382679A5021887509 @default.
- W4313382679 hasAuthorship W4313382679A5023203708 @default.
- W4313382679 hasAuthorship W4313382679A5043409022 @default.
- W4313382679 hasAuthorship W4313382679A5089241426 @default.
- W4313382679 hasConcept C100701293 @default.
- W4313382679 hasConcept C104317684 @default.
- W4313382679 hasConcept C127716648 @default.
- W4313382679 hasConcept C203014093 @default.
- W4313382679 hasConcept C2776090121 @default.
- W4313382679 hasConcept C2776178377 @default.
- W4313382679 hasConcept C2777003663 @default.
- W4313382679 hasConcept C2778170410 @default.
- W4313382679 hasConcept C2779919695 @default.
- W4313382679 hasConcept C502942594 @default.
- W4313382679 hasConcept C51785407 @default.
- W4313382679 hasConcept C54355233 @default.
- W4313382679 hasConcept C59822182 @default.
- W4313382679 hasConcept C81444415 @default.
- W4313382679 hasConcept C86803240 @default.
- W4313382679 hasConcept C8891405 @default.
- W4313382679 hasConcept C95444343 @default.
- W4313382679 hasConceptScore W4313382679C100701293 @default.
- W4313382679 hasConceptScore W4313382679C104317684 @default.
- W4313382679 hasConceptScore W4313382679C127716648 @default.
- W4313382679 hasConceptScore W4313382679C203014093 @default.
- W4313382679 hasConceptScore W4313382679C2776090121 @default.
- W4313382679 hasConceptScore W4313382679C2776178377 @default.
- W4313382679 hasConceptScore W4313382679C2777003663 @default.
- W4313382679 hasConceptScore W4313382679C2778170410 @default.
- W4313382679 hasConceptScore W4313382679C2779919695 @default.
- W4313382679 hasConceptScore W4313382679C502942594 @default.
- W4313382679 hasConceptScore W4313382679C51785407 @default.
- W4313382679 hasConceptScore W4313382679C54355233 @default.
- W4313382679 hasConceptScore W4313382679C59822182 @default.
- W4313382679 hasConceptScore W4313382679C81444415 @default.
- W4313382679 hasConceptScore W4313382679C86803240 @default.
- W4313382679 hasConceptScore W4313382679C8891405 @default.
- W4313382679 hasConceptScore W4313382679C95444343 @default.
- W4313382679 hasIssue "1_Supplement" @default.
- W4313382679 hasLocation W43133826791 @default.
- W4313382679 hasOpenAccess W4313382679 @default.
- W4313382679 hasPrimaryLocation W43133826791 @default.
- W4313382679 hasRelatedWork W1840251084 @default.
- W4313382679 hasRelatedWork W1904656513 @default.
- W4313382679 hasRelatedWork W1966282784 @default.
- W4313382679 hasRelatedWork W1970396987 @default.
- W4313382679 hasRelatedWork W2031697480 @default.
- W4313382679 hasRelatedWork W2106476266 @default.
- W4313382679 hasRelatedWork W2169997919 @default.
- W4313382679 hasRelatedWork W2375999619 @default.
- W4313382679 hasRelatedWork W2939962952 @default.
- W4313382679 hasRelatedWork W4210744974 @default.
- W4313382679 hasVolume "204" @default.
- W4313382679 isParatext "false" @default.
- W4313382679 isRetracted "false" @default.
- W4313382679 workType "article" @default.