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Decoding the immune checkpoint signatures in human atherosclerosis: implications of type 2 diabetes and lipid-lowering intervention

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE246318 | GEO | 2024/10/07

REPOSITORIES: GEO

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Decoding the immune checkpoint signatures in human atherosclerosis: implications of type 2 diabetes and lipid-lowering intervention [human_PBMC_CITEseq]

Project description:Immune checkpoint inhibitor (ICI) therapies in cancer accelerate atherosclerosis progression. Here, we have charted the landscape of immune checkpoint gene expression and defined the network of disease-relevant interactions with single-cell resolution. We found that signaling through PD-1 and CTLA4 is driven by a population of dendritic cells enriched for FSCN1 that can be derived from peripheral blood cells following anti-PD-1 or -CTLA4 treatment ex vivo. Type 2 diabetes dampened plaque PD-1 and CTLA4 signaling, showing that cardiometabolic comorbidities elicit unique responses to ICIs. Lipid-lowering therapy equalized the intensity and direction of immune checkpoint interactions in human blood, while atherosclerotic mice subjected to a lipid-lowering diet displayed both increased co-inhibitory signaling and a downregulation of inflammatory transcriptional programs in plaques. Our findings underscore the potential of lipid-lowering therapies in stabilizing immune checkpoint interactions and reducing plaque inflammation, offering new insights on atherosclerosis and cardiovascular risks in cancer patients undergoing ICI treatments.

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Decoding the immune checkpoint signatures in human atherosclerosis: implications of type 2 diabetes and lipid-lowering intervention [mouse_plaque_scRNAseq]

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Decoding the immune checkpoint signatures in human atherosclerosis: implications of type 2 diabetes and lipid-lowering intervention [human PBMC scRNA-Seq]

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Decoding the immune checkpoint signatures in human atherosclerosis: implications of type 2 diabetes and lipid-lowering intervention

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Decoding the immune checkpoint signatures in human atherosclerosis: implications of type 2 diabetes and lipid-lowering intervention [human_carotid_plaque]

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Decoding the immune checkpoint signatures in human atherosclerosis: implications of type 2 diabetes and lipid-lowering intervention [mouse_plaque_scRNAseq]

Project description:Decoding the immune checkpoint signatures in human atherosclerosis: implications of type 2 diabetes and lipid-lowering intervention [mouse_plaque_scRNAseq]

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Decoding the immune checkpoint signatures in human atherosclerosis: implications of type 2 diabetes and lipid-lowering intervention [human_PBMC_CITEseq]

Project description:Decoding the immune checkpoint signatures in human atherosclerosis: implications of type 2 diabetes and lipid-lowering intervention [human_PBMC_CITEseq]

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Project description:Decoding the immune checkpoint signatures in human atherosclerosis: implications of type 2 diabetes and lipid-lowering intervention [human PBMC scRNA-Seq]

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| S-EPMC3991560 | biostudies-literature

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