Project description:Purpose: Advanced melanoma patients have poor prognosis. Although immune checkpoint blockade has revolutionized treatment for melanoma patients, majority of patients do not respond. The goal of this research is to evaluate whether epigenetic therapy targeting KDM5B could overcome resistance to immunotherapy. Methods:ChIP-Seq analysis of KDM5B binding on retroelements in mouse melanoma cell line YUMMER1.7. Results: We identified that KDM5B directly bind to retreoelements to repress their expression. Conclusions: Our work characterized ablation of histone demethylase KDM5B in melanoma augments anti-tumor immunity through Upregulation of retroelements.
Project description:Purpose: Advanced melanoma patients have poor prognosis. Although immune checkpoint blockade has revolutionized treatment for melanoma patients, majority of patients do not respond. The goal of this research is to evaluate whether epigenetic therapy targeting KDM5B could overcome resistance to immunotherapy. Methods:ChIP-Seq analysis of KDM5B binding on retroelements in mouse melanoma cell line 1445. Results: We identified that KDM5B directly bind to retreoelements to repress their expression. Conclusions: Our work characterized ablation of histone demethylase KDM5B in melanoma augments anti-tumor immunity through Upregulation of retroelements.
Project description:Purpose: Advanced melanoma patients have poor prognosis. Although immune checkpoint blockade has revolutionized treatment for melanoma patients, majority of patients do not respond. The goal of this research is to evaluate whether epigenetic therapy targeting KDM5B could overcome resistance to immunotherapy. Methods:RNA-Seq analysis of KDM5B KO mouse melanoma cell lines compared to control cells to evaluate whether KDM5B depletion induces activation of retroelements, which subsequently activates type I interferon responses. Mouse studies were conducted to evaluate whether anti-tumor immunity induced by KDM5B loss could overcome immunotherapy resistance. Results: We identified that KDM5B depletion derepress retroelement expression, which subsequently activates type I interferon response and enhances anti-tumor immunity. Loss of KDM5B could overcome resistance to anti-PD-1 immunotherapy. Conclusions: Our work characterized ablation of histone demethylase KDM5B in melanoma augments anti-tumor immunity through Upregulation of retroelements.
Project description:Purpose: Advanced melanoma patients have poor prognosis. Although immune checkpoint blockade has revolutionized treatment for melanoma patients, majority of patients do not respond. The goal of this research is to evaluate whether epigenetic therapy targeting KDM5B could overcome resistance to immunotherapy. Methods:RNA-Seq analysis of KDM5B KO mouse melanoma cell lines compared to control cells to evaluate whether KDM5B depletion induces activation of retroelements, which subsequently activates type I interferon responses. Mouse studies were conducted to evaluate whether anti-tumor immunity induced by KDM5B loss could overcome immunotherapy resistance. Results: We identified that KDM5B depletion derepress retroelement expression, which subsequently activates type I interferon response and enhances anti-tumor immunity. Loss of KDM5B could overcome resistance to anti-PD-1 immunotherapy. Conclusions: Our work characterized ablation of histone demethylase KDM5B in melanoma augments anti-tumor immunity through Upregulation of retroelements.
Project description:Purpose: Advanced melanoma patients have poor prognosis. Although immune checkpoint blockade has revolutionized treatment for melanoma patients, majority of patients do not respond. The goal of this research is to evaluate whether epigenetic therapy targeting KDM5B could overcome resistance to immunotherapy. Methods: ATAC-Seq analysis of mouse melanoma cell line YUMMER1.7. Results: We identified that KDM5B directly bind to retreoelements to repress their expression. Conclusions: Our work characterized ablation of histone demethylase KDM5B in melanoma augments anti-tumor immunity through Upregulation of retroelements.
Project description:Ablation of Histone Demethylase KDM5B in Melanoma Augments Anti-Tumor Immunity through Upregulation of Retroelements [RNA-Seq 1445-Kdm5b KO]
Project description:Ablation of Histone Demethylase KDM5B in Melanoma Augments Anti-Tumor Immunity through Upregulation of Retroelements [RNA-Seq YUMMER1.7-Kdm5b KO]