FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4362534762> ?p ?o ?g. }

• W4362534762 endingPage "2886" @default.
• W4362534762 startingPage "2886" @default.
• W4362534762 abstract "Abstract Background: Recent evidence have indicated several tumor-intrinsic oncogene pathways in T cell exclusion and immune evasion of cancers . In hepatocellular carcinoma (HCC), Wnt/β-catenin (CTNNB1) signaling activation is highly prevalent and has been reported to be associated with an immune avoided tumor microenvironment. ICG-001 is a small molecule inhibitor that prevents β-catenin from binding to cyclic AMP response element-binding protein (CBP) by competitively binding itself to CBP. The inhibition of CBP/β-catenin selectively induces apoptosis in transformed cells and have shown tumor suppressive effects in several cancers. Aim: This study aims to investigate the role of tumor-intrinsic Wnt/β-catenin pathway in controlling the expression of chemoattractants in HCC that influence immune cell migration into the tumor site. Methods: We established a syngeneic C57BL/6 mouse model using a hepatoma murine Hepa1-6 isogenic cell line to allow us to interrogate how gain-of-function CTNNB1 mutation (S45P) affects immune surveillance and response to ICG-001 in HCC. The mice were divided into two groups and were subcutaneously injected with either Hepa1-6 vector (n=29) or Hepa1-6 CTNNB1 (S45P) (n=29). At day 6, each group were subdivided into two treatment groups: ICG-001 and untreated. The effect of ICG-001 on immune infiltrates was investigated by Opal multiplex fluorescent immunohistochemistry (IHC) in formalin-fixed, paraffin-embedded (FFPE) tissues. Results: Untreated mice bearing CTNNB1 (S45P) HCCs (n=15) showed larger tumor growth in comparison to their vector controls (n=14), suggesting CTNNB1 (S45P) conferred a more aggressive clone. After a week of ICG-001 treatment by continuous osmotic pump perfusion, 42.9% (6/14) of CTNNB1 (S45P) mice showed a positive response to ICG-001, where a tumor regressed volume was indicated in 4 mice and stable disease in 2 mice. Progressive disease with continuous tumor growth, on the other hand, was shown in all untreated mice. Multiplex fluorescent IHC of tumors obtained from ICG-001 treated CTNNB1 (S45P) mice showed an increased influx of M1 macrophage and CD8 T cells in the tumor site compared to an immune avoidance phenotype in untreated controls. Accordingly, our vector control group did exhibit response to ICG-001 when compared to their respective untreated groups. Based on these findings, it is plausible that CTNNB1 activation impairs the expression of chemoattractant in HCC, and prevents immune cell migration into the tumor site. Consequently, we further examined tumor tissues for chemokine expressions and found higher levels of CXCL9, CXCL10 and CXCL11 in ICG-001 treated CTNNB1 (S45P) when compared to their untreated control groups. In conclusion, our results suggested Wnt/β-catenin activation plays a role in immune evasion and contribution to a “cold” immune tumor microenvironment in HCC. Citation Format: Aikha Melissa Go Wong, Alissa Michelle Go Wong, Loucia KY Can, Joseph Kwong, Anthony WH Chan, Jinna Chen, Michael Kahn, Nathalie Wong. Investigation of tumor-intrinsic activated Wnt/B-catenin signaling in immune avoidance of HCC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2886." @default.
• W4362534762 created "2023-04-06" @default.
• W4362534762 creator A5013733901 @default.
• W4362534762 creator A5015303746 @default.
• W4362534762 creator A5026788333 @default.
• W4362534762 creator A5031515836 @default.
• W4362534762 creator A5035489872 @default.
• W4362534762 creator A5038166050 @default.
• W4362534762 creator A5044300684 @default.
• W4362534762 creator A5069879052 @default.
• W4362534762 date "2023-04-04" @default.
• W4362534762 modified "2023-09-23" @default.
• W4362534762 title "Abstract 2886: Investigation of tumor-intrinsic activated Wnt/B-catenin signaling in immune avoidance of HCC" @default.
• W4362534762 doi "https://doi.org/10.1158/1538-7445.am2023-2886" @default.
• W4362534762 hasPublicationYear "2023" @default.
• W4362534762 type Work @default.
• W4362534762 citedByCount "1" @default.
• W4362534762 countsByYear W43625347622023 @default.
• W4362534762 crossrefType "journal-article" @default.
• W4362534762 hasAuthorship W4362534762A5013733901 @default.
• W4362534762 hasAuthorship W4362534762A5015303746 @default.
• W4362534762 hasAuthorship W4362534762A5026788333 @default.
• W4362534762 hasAuthorship W4362534762A5031515836 @default.
• W4362534762 hasAuthorship W4362534762A5035489872 @default.
• W4362534762 hasAuthorship W4362534762A5038166050 @default.
• W4362534762 hasAuthorship W4362534762A5044300684 @default.
• W4362534762 hasAuthorship W4362534762A5069879052 @default.
• W4362534762 hasConcept C121608353 @default.
• W4362534762 hasConcept C137620995 @default.
• W4362534762 hasConcept C142724271 @default.
• W4362534762 hasConcept C1491633281 @default.
• W4362534762 hasConcept C203014093 @default.
• W4362534762 hasConcept C204232928 @default.
• W4362534762 hasConcept C2776107976 @default.
• W4362534762 hasConcept C2781018059 @default.
• W4362534762 hasConcept C29537977 @default.
• W4362534762 hasConcept C502942594 @default.
• W4362534762 hasConcept C54355233 @default.
• W4362534762 hasConcept C555283112 @default.
• W4362534762 hasConcept C62478195 @default.
• W4362534762 hasConcept C71924100 @default.
• W4362534762 hasConcept C86803240 @default.
• W4362534762 hasConcept C8891405 @default.
• W4362534762 hasConcept C95444343 @default.
• W4362534762 hasConceptScore W4362534762C121608353 @default.
• W4362534762 hasConceptScore W4362534762C137620995 @default.
• W4362534762 hasConceptScore W4362534762C142724271 @default.
• W4362534762 hasConceptScore W4362534762C1491633281 @default.
• W4362534762 hasConceptScore W4362534762C203014093 @default.
• W4362534762 hasConceptScore W4362534762C204232928 @default.
• W4362534762 hasConceptScore W4362534762C2776107976 @default.
• W4362534762 hasConceptScore W4362534762C2781018059 @default.
• W4362534762 hasConceptScore W4362534762C29537977 @default.
• W4362534762 hasConceptScore W4362534762C502942594 @default.
• W4362534762 hasConceptScore W4362534762C54355233 @default.
• W4362534762 hasConceptScore W4362534762C555283112 @default.
• W4362534762 hasConceptScore W4362534762C62478195 @default.
• W4362534762 hasConceptScore W4362534762C71924100 @default.
• W4362534762 hasConceptScore W4362534762C86803240 @default.
• W4362534762 hasConceptScore W4362534762C8891405 @default.
• W4362534762 hasConceptScore W4362534762C95444343 @default.
• W4362534762 hasIssue "7_Supplement" @default.
• W4362534762 hasLocation W43625347621 @default.
• W4362534762 hasOpenAccess W4362534762 @default.
• W4362534762 hasPrimaryLocation W43625347621 @default.
• W4362534762 hasRelatedWork W1967831691 @default.
• W4362534762 hasRelatedWork W2032430075 @default.
• W4362534762 hasRelatedWork W2167484872 @default.
• W4362534762 hasRelatedWork W2320606495 @default.
• W4362534762 hasRelatedWork W2808352915 @default.
• W4362534762 hasRelatedWork W2884621938 @default.
• W4362534762 hasRelatedWork W2938654413 @default.
• W4362534762 hasRelatedWork W3010213676 @default.
• W4362534762 hasRelatedWork W3031982401 @default.
• W4362534762 hasRelatedWork W4308580438 @default.
• W4362534762 hasVolume "83" @default.
• W4362534762 isParatext "false" @default.
• W4362534762 isRetracted "false" @default.
• W4362534762 workType "article" @default.