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Bulk RNA-seq of CD11b+ cells from MC38 tumours in Kaede transgenic mice

ABSTRACT: Bulk RNA-seq of CD11b+ cells from MC38 tumours in Kaede transgenic mice

PROVIDER: PRJNA1271554 | ENA |

REPOSITORIES: ENA

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			Action	DRS
		Other
	SRR33813626_1.fastq.gz	Fastqsanger.gz
	SRR33813626_2.fastq.gz	Fastqsanger.gz
	SRR33813627_1.fastq.gz	Fastqsanger.gz
	SRR33813627_2.fastq.gz	Fastqsanger.gz

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scRNA-seq reveals the temporal dynamics of NK cells in subcutaneous MC38-Ova murine tumours

Project description:We combined scRNA-seq and a photoconvertible Kaede transgenic mouse tumour model to study the temporal dynamics of NK cells in murine tumours.

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Bulk RNA-seq of CD11b+ cells from MC38 tumours in Kaede transgenic mice

Project description:Tumour-associated macrophages (TAMs) are a universal feature of cancers but variably influence outcome and treatment responses. Here, we used a photoconvertible mouse to distinguish newly entering, monocyte-derived (md)TAMs that were enriched at the tumour core, from resident-like (r)TAMs that localised with fibroblasts at the tumour–normal interface. The mdTAM pool was highly dynamic and continually replenished by circulating monocytes. Upon tumour entry, these monocytes differentiated down two divergent fate trajectories distinguished by the expression of MHC class II. MHC-II+ mdTAMs were functionally distinct from MHC-II– mdTAMs, demonstrating increased capacity for endocytosis and FcγR-mediated phagocytosis, as well as pro-inflammatory cytokine production. Both mdTAM subsets showed reduced expression of inflammatory transcripts and increased expression of PD-L1 with increasing tumour dwell-time. Treatment with anti-PD-L1 skewed mdTAM differentiation towards the MHC-II+ fate and attenuated the anti-inflammatory effects of the tumour environment. Anti-PD-L1 enhanced mdTAM–CD4+ T-cell interactions, establishing an IFNγ-CXCL9/10-dependent positive feedback loop. Altogether, these data resolve distinct temporal, spatial and functional properties of TAMs, and provide evidence of subset-specific effects of PD-L1 blockade.

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