FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4366242868> ?p ?o ?g. }

• W4366242868 endingPage "864" @default.
• W4366242868 startingPage "849" @default.
• W4366242868 abstract "The treatment of patients with metastatic melanoma with immune checkpoint inhibitors (ICI) leads to impressive response rates but primary and secondary resistance to ICI reduces progression-free survival. Novel strategies that interfere with resistance mechanisms are key to further improve patient outcome during ICI therapy. P53 is often inactivated by mouse-double-minute-2 (MDM2), which may decrease immunogenicity of melanoma cells. We analyzed primary patient-derived melanoma cell lines, performed bulk sequencing analysis of patient-derived melanoma samples, and used melanoma mouse models to investigate the role of MDM2-inhibition for enhanced ICI therapy. We found increased expression of IL15 and MHC-II in murine melanoma cells upon p53 induction by MDM2-inhibition. MDM2-inhibitor induced MHC-II and IL15-production, which was p53 dependent as Tp53 knockdown blocked the effect. Lack of IL15-receptor in hematopoietic cells or IL15 neutralization reduced the MDM2-inhibition/p53-induction-mediated antitumor immunity. P53 induction by MDM2-inhibition caused anti-melanoma immune memory as T cells isolated from MDM2-inhibitor-treated melanoma-bearing mice exhibited anti-melanoma activity in secondary melanoma-bearing mice. In patient-derived melanoma cells p53 induction by MDM2-inhibition increased IL15 and MHC-II. IL15 and CIITA expressions were associated with a more favorable prognosis in patients bearing WT but not TP53-mutated melanoma.MDM2-inhibition represents a novel strategy to enhance IL15 and MHC-II-production, which disrupts the immunosuppressive tumor microenvironment. On the basis of our findings, a clinical trial combining MDM2-inhibition with anti-PD-1 immunotherapy for metastatic melanoma is planned." @default.
• W4366242868 created "2023-04-20" @default.
• W4366242868 creator A5006320590 @default.
• W4366242868 creator A5007604975 @default.
• W4366242868 creator A5009680251 @default.
• W4366242868 creator A5012722789 @default.
• W4366242868 creator A5014072371 @default.
• W4366242868 creator A5025572775 @default.
• W4366242868 creator A5031480514 @default.
• W4366242868 creator A5033325546 @default.
• W4366242868 creator A5034128863 @default.
• W4366242868 creator A5038897780 @default.
• W4366242868 creator A5039624899 @default.
• W4366242868 creator A5040491715 @default.
• W4366242868 creator A5051381496 @default.
• W4366242868 creator A5051595544 @default.
• W4366242868 creator A5059011363 @default.
• W4366242868 creator A5059867518 @default.
• W4366242868 creator A5075546987 @default.
• W4366242868 creator A5080486436 @default.
• W4366242868 creator A5082422552 @default.
• W4366242868 creator A5084803299 @default.
• W4366242868 creator A5084826274 @default.
• W4366242868 creator A5089415620 @default.
• W4366242868 date "2023-04-18" @default.
• W4366242868 modified "2023-10-17" @default.
• W4366242868 title "MDM2 Inhibition Enhances Immune Checkpoint Inhibitor Efficacy by Increasing IL15 and MHC Class II Production" @default.
• W4366242868 cites W1973767497 @default.
• W4366242868 cites W1990267747 @default.
• W4366242868 cites W2053967595 @default.
• W4366242868 cites W2067526967 @default.
• W4366242868 cites W2097933346 @default.
• W4366242868 cites W2098748257 @default.
• W4366242868 cites W2100494757 @default.
• W4366242868 cites W2120072658 @default.
• W4366242868 cites W2138397823 @default.
• W4366242868 cites W2138657695 @default.
• W4366242868 cites W2142954961 @default.
• W4366242868 cites W2163188200 @default.
• W4366242868 cites W2166662937 @default.
• W4366242868 cites W2253928581 @default.
• W4366242868 cites W2295526061 @default.
• W4366242868 cites W2301707196 @default.
• W4366242868 cites W2572174216 @default.
• W4366242868 cites W2606851967 @default.
• W4366242868 cites W2780852610 @default.
• W4366242868 cites W2788680157 @default.
• W4366242868 cites W2883970691 @default.
• W4366242868 cites W2900587291 @default.
• W4366242868 cites W2909486828 @default.
• W4366242868 cites W2942610007 @default.
• W4366242868 cites W2979874482 @default.
• W4366242868 cites W3015496887 @default.
• W4366242868 cites W3042846071 @default.
• W4366242868 cites W3095200063 @default.
• W4366242868 cites W3124390312 @default.
• W4366242868 cites W3130710766 @default.
• W4366242868 cites W3136307660 @default.
• W4366242868 cites W3180654212 @default.
• W4366242868 cites W4225563096 @default.
• W4366242868 cites W4285798901 @default.
• W4366242868 cites W4295837502 @default.
• W4366242868 doi "https://doi.org/10.1158/1541-7786.mcr-22-0898" @default.
• W4366242868 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37071397" @default.
• W4366242868 hasPublicationYear "2023" @default.
• W4366242868 type Work @default.
• W4366242868 citedByCount "0" @default.
• W4366242868 crossrefType "journal-article" @default.
• W4366242868 hasAuthorship W4366242868A5006320590 @default.
• W4366242868 hasAuthorship W4366242868A5007604975 @default.
• W4366242868 hasAuthorship W4366242868A5009680251 @default.
• W4366242868 hasAuthorship W4366242868A5012722789 @default.
• W4366242868 hasAuthorship W4366242868A5014072371 @default.
• W4366242868 hasAuthorship W4366242868A5025572775 @default.
• W4366242868 hasAuthorship W4366242868A5031480514 @default.
• W4366242868 hasAuthorship W4366242868A5033325546 @default.
• W4366242868 hasAuthorship W4366242868A5034128863 @default.
• W4366242868 hasAuthorship W4366242868A5038897780 @default.
• W4366242868 hasAuthorship W4366242868A5039624899 @default.
• W4366242868 hasAuthorship W4366242868A5040491715 @default.
• W4366242868 hasAuthorship W4366242868A5051381496 @default.
• W4366242868 hasAuthorship W4366242868A5051595544 @default.
• W4366242868 hasAuthorship W4366242868A5059011363 @default.
• W4366242868 hasAuthorship W4366242868A5059867518 @default.
• W4366242868 hasAuthorship W4366242868A5075546987 @default.
• W4366242868 hasAuthorship W4366242868A5080486436 @default.
• W4366242868 hasAuthorship W4366242868A5082422552 @default.
• W4366242868 hasAuthorship W4366242868A5084803299 @default.
• W4366242868 hasAuthorship W4366242868A5084826274 @default.
• W4366242868 hasAuthorship W4366242868A5089415620 @default.
• W4366242868 hasBestOaLocation W43662428681 @default.
• W4366242868 hasConcept C170627219 @default.
• W4366242868 hasConcept C203014093 @default.
• W4366242868 hasConcept C207936829 @default.
• W4366242868 hasConcept C2776192174 @default.
• W4366242868 hasConcept C2777658100 @default.
• W4366242868 hasConcept C2777701055 @default.
• W4366242868 hasConcept C502942594 @default.

• next