Tumor endothelial cell autophagy is a key vascular-immune checkpoint in melanoma.

ABSTRACT: Tumor endothelial cells (TECs) actively repress inflammatory responses and maintain an immune-excluded tumor phenotype. However, the molecular mechanisms that sustain TEC-mediated immunosuppression remain largely elusive. Here, we show that autophagy ablation in TECs boosts antitumor immunity by supporting infiltration and effector function of T-cells, thereby restricting melanoma growth. In melanoma-bearing mice, loss of TEC autophagy leads to the transcriptional expression of an immunostimulatory/inflammatory TEC phenotype driven by heightened NF-kB and STING signaling. In line, single-cell transcriptomic datasets from melanoma patients disclose an enriched Inflammatory^High /Autophagy^Low TEC phenotype in correlation with clinical responses to immunotherapy, and resp

SUBMITTER: Verhoeven J 

PROVIDER: S-EPMC10701618 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature