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Conserved transcriptional connectivity of regulatory T cells in the tumor microenvironment informs novel combination cancer therapy strategies

ABSTRACT: Conserved transcriptional connectivity of regulatory T cells in the tumor microenvironment informs novel combination cancer therapy strategies

PROVIDER: PRJNA834811 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR19067500_1.fastq.gz	Fastqsanger.gz
	SRR19067500_2.fastq.gz	Fastqsanger.gz
	SRR19067501_1.fastq.gz	Fastqsanger.gz
	SRR19067501_2.fastq.gz	Fastqsanger.gz
	SRR19067502_1.fastq.gz	Fastqsanger.gz

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Conserved transcriptional connectivity of regulatory T cells in the tumor microenvironment informs novel combination cancer therapy strategies [mouse]

Project description:Conserved transcriptional connectivity of regulatory T cells in the tumor microenvironment informs novel combination cancer therapy strategies [mouse]

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Conserved transcriptional connectivity of regulatory T cells in the tumor microenvironment informs novel combination cancer therapy strategies [visium]

Project description:Conserved transcriptional connectivity of regulatory T cells in the tumor microenvironment informs novel combination cancer therapy strategies [visium]

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Conserved transcriptional connectivity of regulatory T cells in the tumor microenvironment informs novel combination cancer therapy strategies [mouse]

Project description:While regulatory T (Treg) cells are traditionally viewed as professional suppressors of antigen presenting and effector T cells in both autoimmunity and cancer, recent findings of distinct Treg functions in tissue maintenance suggest that their regulatory purview extends to a wider range of cells and is broader than previously assumed. To elucidate tumoral Treg “connectivity” to diverse tumor-supporting accessory cell types, we explored immediate early changes in their single cell transcriptomes upon punctual Treg depletion in experimental lung cancer and injury-induced inflammation. Prior to any notable T cell activation and inflammation, fibroblasts, endothelial and myeloid cells exhibited pronounced changes in their gene expression in both cancer and injury settings. Factor analysis revealed shared Treg-dependent gene programs, foremost, prominent upregulation of VEGF signaling-related genes upon Treg deprivation in either setting, as well as in Treg-poor vs Treg-rich human lung adenocarcinomas. Accordingly, punctual Treg depletion combined with short-term VEGF blockade showed markedly improved control of PD-1 blockade-resistant lung adenocarcinoma progression in mice compared to the corresponding monotherapies, highlighting a promising factor-based querying approach to elucidating novel rational combination treatments of solid organ cancers.

2023-05-01 | GSE202157 | GEO

Conserved transcriptional connectivity of regulatory T cells in the tumor microenvironment informs novel combination cancer therapy strategies [visium]

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Conserved transcriptional connectivity of regulatory T cells in the tumor microenvironment informs novel combination cancer therapy strategies

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

2023-05-03 | GSE202159 | GEO

Conserved transcriptional connectivity of regulatory T cells in the tumor microenvironment informs new combination cancer therapy strategies.

Project description: Not available

| S-EPMC10232368 | biostudies-literature

Conserved replication strategies facilitate the cross-species

Project description:Conserved replication strategies facilitate the cross-species

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Bisulphite-sequencing of chromatin immunoprecipitated DNA directly informs methylation status of histone-modified DNA

Project description:This SuperSeries is composed of the following subset Series: GSE30558: Bisulphite-sequencing of chromatin immunoprecipitated DNA (BisChiP-seq) directly informs methylation status GSE34340: Bisulphite sequencing of native LNCaP and PrEC DNA [methylation array] Refer to individual Series

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A clinically applicable connectivity signature for glioblastoma includes the tumor network driver CHI3L1

Project description:Tumor microtubes (TMs) connect glioma cells to a network with considerable relevance for tumor progression and therapy resistance. The determination of TM-interconnectivity in individual tumors has been challenging and the impact on patient survival unresolved. Here, a connectivity signature from single-cell RNA-sequenced (scRNA-Seq) xenografted primary glioblastoma (GB) cells has been established using a dye uptake methodology, confirmed with recording of cellular calcium epochs and validated with clinical correlations. Astrocyte-like and mesenchymal-like GB cells have the highest connectivity signature scores in scRNA-sequenced patient-derived xenografts and patient samples. In large GB cohorts, network connectivity correlated with the mesenchymal subtype and dismal patient survival. CHI3L1 has been identified and validated as a robust molecular marker of connectivity with functional relevance. The connectivity signature allows novel insights into brain tumor biology, provides a proof-of-principle that tumor cell TM-connectivity is relevant for patients’ prognosis, and serves as a robust prognostic biomarker.

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Macromolecular connectivity landscape of mammalian brain

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