| First Author | Verhoeven J | Year | 2023 |
| Journal | EMBO Mol Med | Volume | 15 |
| Issue | 12 | Pages | e18028 |
| PubMed ID | 38009521 | Mgi Jnum | J:343461 |
| Mgi Id | MGI:7564710 | Doi | 10.15252/emmm.202318028 |
| Citation | Verhoeven J, et al. (2023) Tumor endothelial cell autophagy is a key vascular-immune checkpoint in melanoma. EMBO Mol Med 15(12):e18028 |
| abstractText | 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 responders exhibit an increased presence of inflamed vessels interfacing with infiltrating CD8(+) T-cells. Mechanistically, STING-dependent immunity in TECs is not critical for the immunomodulatory effects of autophagy ablation, since NF-kB-driven inflammation remains functional in STING/ATG5 double knockout TECs. Hence, our study identifies autophagy as a principal tumor vascular anti-inflammatory mechanism dampening melanoma antitumor immunity. |
