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P16-dependent upregulation of PD-L1 impairs immunosurveillance of senescent cells [RNA-seq: Lung Alveolar Macrophages]

ABSTRACT: The accumulation of senescent cells promotes aging, but a molecular mechanism that senescent cells use to evade immune clearance and accumulate remains to be elucidated. Here, we report that p16-positive senescent cells upregulate the immune checkpoint protein programmed death-ligand 1 (PD-L1) to accumulate in aging and chronic inflammation. p16-mediated inhibition of CDK4/6 promotes PD-L1 stability in senescent cells via the downregulation of ubiquitin-dependent degradation. p16 expression in infiltrating macrophages induces an immunosuppressive environment that can contribute to an increased burden of senescent cells. Treatment with immunostimulatory anti-PD-L1 antibody enhances the cytotoxic T cell activity and leads to the elimination of p16, PD-L1-positive cells. Our study uncovers a molecular mechanism of p16-dependent regulation of PD-L1 protein stability in senescent cells and reveals the potential of PD-L1 as a target for treating senescence-mediated age-associated diseases.

ORGANISM(S): Mus musculus

PROVIDER: GSE225285 | GEO | 2024/02/14

REPOSITORIES: GEO

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p16-dependent upregulation of PD-L1 impairs immunosurveillance of senescent cells [RNA-seq: Lung Epithelial Cells]

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