Cited 0 times in Scipus Cited Count

Targeting GAS6/AXL signaling improves the response to immunotherapy by restoring the anti-immunogenic tumor microenvironment in gastric cancer

DC Field Value Language
dc.contributor.authorKim, TH-
dc.contributor.authorLee, D-
dc.contributor.authorOh, HJ-
dc.contributor.authorHam, IH-
dc.contributor.authorLee, DM-
dc.contributor.authorLee, Y-
dc.contributor.authorZhang, Z-
dc.contributor.authorKe, D-
dc.contributor.authorHur, H-
dc.date.accessioned2024-01-23T07:54:32Z-
dc.date.available2024-01-23T07:54:32Z-
dc.date.issued2023-
dc.identifier.issn0024-3205-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/32095-
dc.description.abstractAims: Immunotherapy has shown remarkable effects on several malignancies; however, its impact on gastric cancers has been limited. Therefore, a novel strategy to overcome resistance to immunotherapy is required. In this study, we compared the gene expression profiles of two murine GC cell lines that exhibited different effects on tumor immunity. The functions of specific genes related to negative tumor immunity and the impact of a specific inhibitor were evaluated in syngeneic GC mouse models. Materials and methods: RT-PCR and Western blotting validated Gas6 and AXL expression in murine cell lines. RT-PCR compared YTN16 and YTN3 GC cell's impact on T cell activation. AXL, the receptor for GAS6 in YTN16, was validated by western blotting. Gas6 was inhibited in YTN16 cells using shRNA, and then the gene expression pattern, effects to T cell activation, and tumor growth were assessed. YTN16 cells were injected into mice and treated with CCB-3233, anti-PD-1 antibody, or both. Immunohistochemistry and flow cytometry evaluated tumor-infiltrating immune cells. Key findings: YTN16 cells expressed more Gas6 and had reduced T cell activation compared to YTN3 cells. AXL activation was higher in YTN16. CCB-3233 reduced AXL phosphorylation. Knocking down Gas6 in YTN16 reduced immunosuppression-related genes and increased tumor-infiltrating T cells. Combined CCB-3233 and anti-PD-1 treatment reduced tumor growth and increased T-cell infiltration. Human GC data revealed a negative correlation between GAS6 and immune activation-related genes. Significance: The GAS6/AXL pathway contributes to immunotherapy resistance in GC. Targeting this pathway may be a novel therapeutic strategy.-
dc.language.isoen-
dc.subject.MESHAnimals-
dc.subject.MESHAxl Receptor Tyrosine Kinase-
dc.subject.MESHHumans-
dc.subject.MESHImmunotherapy-
dc.subject.MESHMice-
dc.subject.MESHProto-Oncogene Proteins-
dc.subject.MESHReceptor Protein-Tyrosine Kinases-
dc.subject.MESHStomach Neoplasms-
dc.subject.MESHTumor Microenvironment-
dc.titleTargeting GAS6/AXL signaling improves the response to immunotherapy by restoring the anti-immunogenic tumor microenvironment in gastric cancer-
dc.typeArticle-
dc.identifier.pmid37952835-
dc.subject.keywordGastric Cancer-
dc.subject.keywordGrowth arrest-specific 6-
dc.subject.keywordImmune checkpoint inhibitor-
dc.subject.keywordSyngeneic mouse-
dc.subject.keywordTumor immunity-
dc.contributor.affiliatedAuthorHam, IH-
dc.contributor.affiliatedAuthorHur, H-
dc.type.localJournal Papers-
dc.identifier.doi10.1016/j.lfs.2023.122230-
dc.citation.titleLife sciences-
dc.citation.volume335-
dc.citation.date2023-
dc.citation.startPage122230-
dc.citation.endPage122230-
dc.identifier.bibliographicCitationLife sciences, 335. : 122230-122230, 2023-
dc.embargo.liftdate9999-12-31-
dc.embargo.terms9999-12-31-
dc.identifier.eissn1879-0631-
dc.relation.journalidJ000243205-
Appears in Collections:
Journal Papers > Research Organization > Inflamm-aging Translational Research Center
Journal Papers > School of Medicine / Graduate School of Medicine > Surgery
Files in This Item:
There are no files associated with this item.

qrcode

해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse