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KDM5A epigenetically orchestrates MHC-I associated anti-tumor immunity of immunotherapy [tumor-CUTTag]

ABSTRACT: KDM5A epigenetically orchestrates MHC-I associated anti-tumor immunity of immunotherapy [tumor-CUTTag]

PROVIDER: PRJNA1077952 | ENA |

REPOSITORIES: ENA

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KDM5A epigenetically orchestrates MHC-I associated anti-tumor immunity of immunotherapy [tumor-CUTTag]

Project description:Immune checkpoint blockade (ICB) therapy revolutionized cancer treatment, but many patients with impaired MHC-I expression remain refractory. Histone methylation was involved in anti-tumor immunity of ICB. However, the link between histone methylation and MHC-I regulation and the related mechanisms are poorly understood. Here we show that KDM5A, an H3K4 demethylase that is critical for MHC-I expression and associated antigen presentation capacity, induces robust immune response and enhances ICB efficacy. Mechanistically, KDM5A upregulates IFN-gamma/STAT1-mediated MHC-I expression via directly binding and suppressing Scos1 in tumor cells. The genes encoding the lysosomal cathepsins are recognized and up-regulated by KDM5A, resulting in enhanced antigen-presentation abilities of both tumor cells and dendritic cells. Furthermore, pharmacological enhancing KDM5A improves response to anti-PD-1 therapy. These investigations demonstrate that enhancing KDM5A triggers MHC-associated antigen presentation of both tumor cells and DCs simultaneously to boost antitumor immunity, thus represents a candidate ICB sensitizer.

2025-08-30 | GSE256056 | GEO

KDM5A epigenetically orchestrates MHC-I associated anti-tumor immunity of immunotherapy [DC-CUTTag]

Project description:KDM5A epigenetically orchestrates MHC-I associated anti-tumor immunity of immunotherapy [DC-CUTTag]

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KDM5A epigenetically orchestrates MHC-I associated anti-tumor immunity of immunotherapy [DC-CUTTag]

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KDM5A epigenetically orchestrates MHC-I associated anti-tumor immunity of immunotherapy [DC RNA-seq]

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KDM5A epigenetically orchestrates MHC-I associated anti-tumor immunity of immunotherapy

Project description:KDM5A epigenetically orchestrates MHC-I associated anti-tumor immunity of immunotherapy

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Gene expression profiles of KDM5A-/- MEFs with wild-type KDM5A or KDM5A-H483A mutant

Project description:Gene expression profiles of Immortalized KDM5A-/- MEFs with re-introduction of wild-type KDM5A or KDM5A-H483A mutant.

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KDM5A inhibits anti-tumor immune response through downregulation of antigen presentation pathway in ovarian cancer [CUT&RUN]

Project description:The infiltration of effector CD8+ T cells into tumors is one of the major predictors of clinical outcome for epithelial ovarian cancer (EOC) patients. Immune cell infiltration is a complex process that could be affected by the epigenetic makeup of the tumor. Here, we demonstrate that a lysine 4 histone H3 (H3K4) demethylase KDM5A impairs immune cell infiltration and inhibits anti-tumor immune response. Mechanistically, KDM5A silences genes involved in antigen processing and presentation pathway. Antigen processing and presentation is a critical step that is required for CD8+ T cells infiltration and activation of CD8+ T cell mediated anti-tumor immune response. KDM5A inhibition restores the expression of antigen presentation pathway in vitro and promotes anti-tumor immune response mediated by CD8+ T cells in vivo in a syngeneic EOC mouse model. Notably, a negative correlation between expression of KDM5A and genes involved in antigen processing and presentation pathway such as HLA-A and HLA-B is observed in the majority of cancer types. In summary, our results establish KDM5A as a regulator of CD8+ T cells tumor infiltration and demonstrate that KDM5A inhibition is a novel therapeutic strategy aiming to boost anti-tumor immune response.

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KDM5A inhibits anti-tumor immune response through downregulation of antigen presentation pathway in ovarian cancer [RNA-seq]

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Project description:KDM5A epigenetically orchestrates MHC-I associated anti-tumor immunity of immunotherapy

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KDM5A epigenetically orchestrates MHC-I associated anti-tumor immunity of immunotherapy

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-03-31 | GSE256057 | GEO