Matches in SemOpenAlex for { <https://semopenalex.org/work/W4308726976> ?p ?o ?g. }
Showing items 1 to 73 of
73
with 100 items per page.
- W4308726976 abstract "Abstract Background Accumulating evidence suggests that cancer-associated fibroblast (CAF) autophagy is crucial in tumor development and may be a therapeutic target for pancreatic ductal adenocarcinoma (PDAC). However, the role of CAFs autophagy during immune surveillance and cancer immunotherapy is unclear. Methods In vivo efficacy and mechanistic studies, using ATG5f/f α-SMAcreERT2 mice, KPC-genetically engineered mouse model (GEMM) mice, C57BL/6 mice and nude mice with KPC cell‑derived orthotopic tumors, employed immune checkpoint blockades (ICBs) and gemcitabine. Mass cytometry (CyTOF), immunohistochemistry (IHC), and flow cytometry analyzed local and systemic alterations in the immunophenotype. The regulatory effects of CAFs autophagy on tumour PD-L1 and its downstream signaling were analyzed by RNA-seq, 4D mass spectrometer (MS), IP-MS, western blotting, GST-pulldown, immunofluorescence (IF), IHC, and flow cytometry. Results The present study revealed that the inhibition of CAF autophagy suppresses in vivo tumor development in immune-deficient xenografts. This deletion compromises anti-tumor immunity and anti-tumor efficacy both in vitro and in vivo by upregulating PD-L1 levels in an immune-competent mouse model. A deletion in CAF autophagy reduced the production of interleukin 6, disrupting high desmoplastic TME and decreasing USP14 expression at the transcription level in pancreatic cancer cells. We further identify USP14 as the post-translational factor responsible for downregulating PD-L1 expression by removing K63 linked-ubiquitination at the K280 residue. Finally, chloroquine diphosphate-loaded mesenchymal stem cell (MSC)-liposome, by accurately targeting CAFs, inhibited CAF autophagy, improving the efficacy of immunochemotherapy to combat pancreatic cancer. Conclusions Targeting CAFs autophagy disrupt the desmoplastic and immunosuppressive TME to enhance the efficacy of immunochemotherapy by inhibiting adaptive immune resistance." @default.
- W4308726976 created "2022-11-15" @default.
- W4308726976 creator A5004969274 @default.
- W4308726976 creator A5020463692 @default.
- W4308726976 creator A5026242985 @default.
- W4308726976 creator A5037458498 @default.
- W4308726976 creator A5043001105 @default.
- W4308726976 creator A5053013530 @default.
- W4308726976 creator A5056443773 @default.
- W4308726976 creator A5057978323 @default.
- W4308726976 creator A5076590187 @default.
- W4308726976 creator A5080777187 @default.
- W4308726976 date "2022-11-09" @default.
- W4308726976 modified "2023-09-29" @default.
- W4308726976 title "Targeting cancer-associated fibroblast autophagy renders pancreatic cancer eradicable with immunochemotherapy by inhibiting adaptive immune resistance" @default.
- W4308726976 doi "https://doi.org/10.21203/rs.3.rs-2224090/v1" @default.
- W4308726976 hasPublicationYear "2022" @default.
- W4308726976 type Work @default.
- W4308726976 citedByCount "0" @default.
- W4308726976 crossrefType "posted-content" @default.
- W4308726976 hasAuthorship W4308726976A5004969274 @default.
- W4308726976 hasAuthorship W4308726976A5020463692 @default.
- W4308726976 hasAuthorship W4308726976A5026242985 @default.
- W4308726976 hasAuthorship W4308726976A5037458498 @default.
- W4308726976 hasAuthorship W4308726976A5043001105 @default.
- W4308726976 hasAuthorship W4308726976A5053013530 @default.
- W4308726976 hasAuthorship W4308726976A5056443773 @default.
- W4308726976 hasAuthorship W4308726976A5057978323 @default.
- W4308726976 hasAuthorship W4308726976A5076590187 @default.
- W4308726976 hasAuthorship W4308726976A5080777187 @default.
- W4308726976 hasBestOaLocation W43087269761 @default.
- W4308726976 hasConcept C121608353 @default.
- W4308726976 hasConcept C190283241 @default.
- W4308726976 hasConcept C203014093 @default.
- W4308726976 hasConcept C203522944 @default.
- W4308726976 hasConcept C2776107976 @default.
- W4308726976 hasConcept C2777701055 @default.
- W4308726976 hasConcept C2780210213 @default.
- W4308726976 hasConcept C502942594 @default.
- W4308726976 hasConcept C54355233 @default.
- W4308726976 hasConcept C553184892 @default.
- W4308726976 hasConcept C55493867 @default.
- W4308726976 hasConcept C86803240 @default.
- W4308726976 hasConcept C8891405 @default.
- W4308726976 hasConceptScore W4308726976C121608353 @default.
- W4308726976 hasConceptScore W4308726976C190283241 @default.
- W4308726976 hasConceptScore W4308726976C203014093 @default.
- W4308726976 hasConceptScore W4308726976C203522944 @default.
- W4308726976 hasConceptScore W4308726976C2776107976 @default.
- W4308726976 hasConceptScore W4308726976C2777701055 @default.
- W4308726976 hasConceptScore W4308726976C2780210213 @default.
- W4308726976 hasConceptScore W4308726976C502942594 @default.
- W4308726976 hasConceptScore W4308726976C54355233 @default.
- W4308726976 hasConceptScore W4308726976C553184892 @default.
- W4308726976 hasConceptScore W4308726976C55493867 @default.
- W4308726976 hasConceptScore W4308726976C86803240 @default.
- W4308726976 hasConceptScore W4308726976C8891405 @default.
- W4308726976 hasLocation W43087269761 @default.
- W4308726976 hasOpenAccess W4308726976 @default.
- W4308726976 hasPrimaryLocation W43087269761 @default.
- W4308726976 hasRelatedWork W2086604883 @default.
- W4308726976 hasRelatedWork W2921982580 @default.
- W4308726976 hasRelatedWork W3025154575 @default.
- W4308726976 hasRelatedWork W3028822667 @default.
- W4308726976 hasRelatedWork W3093610262 @default.
- W4308726976 hasRelatedWork W4283521860 @default.
- W4308726976 hasRelatedWork W4286005638 @default.
- W4308726976 hasRelatedWork W4286629873 @default.
- W4308726976 hasRelatedWork W4297348332 @default.
- W4308726976 hasRelatedWork W4362003594 @default.
- W4308726976 isParatext "false" @default.
- W4308726976 isRetracted "false" @default.
- W4308726976 workType "article" @default.