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Cancer cells impair monocyte-mediated intratumoral T cell stimulation [YUMM3.3]

ABSTRACT: Cancer cells impair monocyte-mediated intratumoral T cell stimulation [YUMM3.3]

PROVIDER: PRJNA1009802 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25764109_1.fastq.gz	Fastqsanger.gz
	SRR25764109_2.fastq.gz	Fastqsanger.gz
	SRR25764110_1.fastq.gz	Fastqsanger.gz
	SRR25764110_2.fastq.gz	Fastqsanger.gz

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Cancer cells impair monocyte-mediated intratumoral T cell stimulation

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Cancer cells impair monocyte-mediated intratumoral T cell stimulation [YUMM3.3]

Project description:The tumor microenvironment (TME) is programmed by cancer cells and critically influences antitumor immune responses. Within the TME, CD8+ T cells undergo full effector differentiation and acquire cytotoxic antitumor functions in specialized niches. While interactions with conventional type-1 dendritic cells (cDC1s) have been implicated in this proces, underlying cellular players and molecular mechanisms remain incompletely understood. Here, we show that inflammatory monocytes can adopt a critical role in intratumoral T cell stimulation. They express Cxcl9, Cxcl10 and Il15, but as opposed to cDC1s that cross-present antigens, inflammatory monocytes obtain and present peptide-major histocompatibility complex class I (pMHCI) complexes from tumor cells through “cross-dressing”. Hyperactivation of MAPK signaling in cancer cells hampers this process by coordinately blunting the production of type I interferon (IFN-I) and inducing the secretion of prostaglandin E2 (PGE2), impairing the inflammatory monocyte state and intratumoral T cell stimulation. Enhancing IFN-I production and blocking PGE2 secretion restores this process and thereby re-sensitizes tumors to T cell-mediated immunity. Together, our work uncovers a central role of inflammatory monocytes in intratumoral T cell stimulation, elucidates how oncogenic signaling disrupts T cell responses via counter-regulation of PGE2 and IFN-I, and proposes rational combination therapies to enhance immunotherapies.

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Cancer cells impair monocyte-mediated intratumoral T cell stimulation [R15287 YUMM1.7 RTT IRF37/COX2i/AZA]

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