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Targeted inducible delivery of immunoactivating cytokines reprograms glioblastoma microenvironment and inhibits growth in mouse models

ABSTRACT: Targeted inducible delivery of immunoactivating cytokines reprograms glioblastoma microenvironment and inhibits growth in mouse models

PROVIDER: PRJNA812008 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14369917.fastq.gz	Fastqsanger.gz
	SRR14369918.fastq.gz	Fastqsanger.gz
	SRR14369919.fastq.gz	Fastqsanger.gz
	SRR14369920.fastq.gz	Fastqsanger.gz
	SRR14369921.fastq.gz	Fastqsanger.gz

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Targeted inducible delivery of immunoactivating cytokines reprograms glioblastoma microenvironment and inhibits growth in mouse models [scRNA-seq]

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Project description:We exploited a lentiviral vector-based platform to engineer hematopoietic stem cells ex vivo with the aim of releasing, via their tumor-infiltrating monocyte/macrophage progeny, IFN-a or IL-12 at the tumor site in a spatial and temporal regulated manner. Taking advantage of a syngeneic GBM mouse model, we showed that inducible release of IFN-a within the TME achieved robust tumor inhibition up to eradication and outperformed systemic treatment with the recombinant protein in terms of efficacy, tolerability and specificity. Single-cell RNAseq of the tumor immune infiltrate revealed reprogramming of the immune microenvironment towards a pro-inflammatory and anti-tumoral state associated with loss of a macrophage subpopulation predicting poor prognosis in human GBM.

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