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

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

PROVIDER: PRJNA800370 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17735745.fastq.gz	Fastqsanger.gz
	SRR17735746.fastq.gz	Fastqsanger.gz
	SRR17735747.fastq.gz	Fastqsanger.gz

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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.

2022-05-02 | GSE194359 | GEO

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

2022-05-02 | GSE194358 | GEO

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

Project description:KDM5A inhibits anti-tumor immune response through downregulation of antigen presentation pathway in ovarian cancer

| PRJNA800360 | ENA

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

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

| PRJNA800371 | ENA

KDM5A Inhibits Antitumor Immune Responses Through Downregulation of the Antigen-Presentation Pathway in Ovarian Cancer.

Project description:The extent to which effector CD8+ T cells infiltrate into tumors is one of the major predictors of clinical outcome for patients with epithelial ovarian cancer (EOC). Immune cell infiltration into EOC is a complex process that could be affected by the epigenetic makeup of the tumor. Here, we have demonstrated that a lysine 4 histone H3 (H3K4) demethylase, (lysine-specific demethylase 5A; KDM5A) impairs EOC infiltration by immune cells and inhibits antitumor immune responses. Mechanistically, we found that KDM5A silenced genes involved in the antigen processing and presentation pathway. KDM5A inhibition restored the expression of genes involved in the antigen-presentation pathway in vitro and promoted antitumor immune responses mediated by CD8+ T cells in vivo in a syngeneic EOC mouse model. A negative correlation between expression of KDM5A and genes involved in the antigen processing and presentation pathway such as HLA-A and HLA-B was observed in the majority of cancer types. In summary, our results establish KDM5A as a regulator of CD8+ T-cell infiltration of tumors and demonstrate that KDM5A inhibition may provide a novel therapeutic strategy to boost antitumor immune responses.

| S-EPMC9357105 | biostudies-literature

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

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

2022-04-29 | GSE194361 | GEO

Expression profiling of human medulloblastoma cell line ONS76 upon siRNA-mediated knockdown of KDM5A/LSD1

Project description:KDM5A/LSD1 is an important epigenetic regulator in medulloblastoma, the most frequent brain tumor of childhood. Here, the response of ONS76 medulloblastoma cells upon siRNA-mediated knockdown of KDM5A is analysed. The expression profile of ONS76 cells upon KDM5A knockdown was compared to mock control. Both conditions were run in triplicate.

2013-08-01 | E-GEOD-43552 | biostudies-arrayexpress

Oligomeric human Aβ1-42 inhibits antigen presentation

Project description:Oligomeric human Aβ1-42 inhibits antigen presentation

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

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.

2024-03-31 | GSE260912 | GEO

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.

2017-02-08 | GSE84309 | GEO