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Epigenetic priming induces cancer testis antigens and human endogenous retroviruses in glioma for enhanced T cell responses at single cell resolution

ABSTRACT: Epigenetic priming induces cancer testis antigens and human endogenous retroviruses in glioma for enhanced T cell responses at single cell resolution

PROVIDER: PRJNA1085730 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28275970_1.fastq.gz	Fastqsanger.gz
	SRR28275970_2.fastq.gz	Fastqsanger.gz
	SRR28275371_1.fastq.gz	Fastqsanger.gz
	SRR28275371_2.fastq.gz	Fastqsanger.gz
	SRR28275971_1.fastq.gz	Fastqsanger.gz

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Epigenetic priming induces cancer testis antigens and human endogenous retroviruses in glioma for enhanced T cell responses at single cell resolution (methylation)

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Epigenetic priming induces cancer testis antigens and human endogenous retroviruses in glioma for enhanced T cell responses at single cell resolution (methylation)

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Epigenetic priming induces cancer testis antigens and human endogenous retroviruses in glioma for enhanced T cell responses at single cell resolution (bulk RNA-Seq)

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Histone H3.3K27M mutation activates multiple cancer/testis antigens

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Epigenetic priming induces cancer testis antigens and human endogenous retroviruses in glioma for enhanced T cell responses at single cell resolution

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

2024-06-03 | GSE261191 | GEO

Dendritic Cells Compare the Similarity of Endogenous and Exogenous Antigens

Project description:Here we demonstrate by the use of extensive controls and stringent statistical analysis that dendritic cells differentially regulate hundreds of different genes based upon sequence similarity of endogenously- and exogenously-loaded antigens and in a T-cell independent fashion. When endogenously and exogenously-derived antigens are identical, dendritic cells upregulate many different components of the Th-1 response, favoring the priming of CD8+ effectors and promulgating cellular immunity. Keywords: Loading methodology comparison

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Epigenetic Induction of Cancer-Testis Antigens and Endogenous Retroviruses at Single-Cell Level Enhances Immune Recognition and Response in Glioma.

Project description:Glioblastoma (GBM) is the most common malignant primary brain tumor and remains incurable. Previous work has shown that systemic administration of Decitabine (DAC) induces sufficient expression of cancer-testis antigens (CTA) in GBM for targeting by adoptive T-cell therapy in vivo. However, the mechanisms by which DAC enhances immunogenicity in GBM remain to be elucidated. Using New York esophageal squamous cell carcinoma 1 (NY-ESO-1) as a representative inducible CTA, we demonstrate in patient tissue, immortalized glioma cells, and primary patient-derived gliomaspheres that basal CTA expression is restricted by promoter hypermethylation in gliomas. DAC treatment of glioma cells specifically inhibits DNA methylation silencing to render NY-ESO-1 and other CTA into inducible tumor antigens at single-cell resolution. Functionally, NY-ESO-1 T-cell receptor-engineered effector cell targeting of DAC-induced antigen in primary glioma cells promotes specific and polyfunctional T-cell cytokine profiles. In addition to induction of CTA, DAC concomitantly reactivates tumor-intrinsic human endogenous retroviruses, interferon response signatures, and MHC-I. Overall, we demonstrate that DAC induces targetable tumor antigen and enhances T-cell functionality against GBM, ultimately contributing to the improvement of targeted immune therapies in glioma.SignificanceThis study dissects the tumor-intrinsic epigenetic and transcriptional mechanisms underlying enhanced T-cell functionality targeting decitabine-induced cancer-testis antigens in glioma. Our findings demonstrate concomitant induction of tumor antigens, reactivation of human endogenous retroviruses, and stimulation of interferon signaling as a mechanistic rationale to epigenetically prime human gliomas to immunotherapeutic targeting.

| S-EPMC11275559 | biostudies-literature

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