دورية أكاديمية
Tumor endothelial cell autophagy is a key vascular‐immune checkpoint in melanoma
| العنوان: | Tumor endothelial cell autophagy is a key vascular‐immune checkpoint in melanoma |
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| المؤلفون: | Jelle Verhoeven, Kathryn A Jacobs, Francesca Rizzollo, Francesca Lodi, Yichao Hua, Joanna Poźniak, Adhithya Narayanan Srinivasan, Diede Houbaert, Gautam Shankar, Sanket More, Marco B Schaaf, Nikolina Dubroja Lakic, Maarten Ganne, Jochen Lamote, Johan Van Weyenbergh, Louis Boon, Oliver Bechter, Francesca Bosisio, Yasuo Uchiyama, Mathieu JM Bertrand, Jean Christophe Marine, Diether Lambrechts, Gabriele Bergers, Madhur Agrawal, Patrizia Agostinis |
| المصدر: | EMBO Molecular Medicine, Vol 15, Iss 12, Pp n/a-n/a (2023) |
| بيانات النشر: | Springer Nature, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Medicine (General) LCC:Genetics |
| مصطلحات موضوعية: | autophagy, cancer, immunotherapy, inflammation, tumor endothelial cells, Medicine (General), R5-920, Genetics, QH426-470 |
| الوصف: | 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 InflammatoryHigh/AutophagyLow 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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1757-4684 1757-4676 |
| Relation: | https://doaj.org/toc/1757-4676; https://doaj.org/toc/1757-4684 |
| DOI: | 10.15252/emmm.202318028 |
| URL الوصول: | https://doaj.org/article/bbcea8700d3946d0a54b3724c68d12c4 |
| رقم الأكسشن: | edsdoj.bbcea8700d3946d0a54b3724c68d12c4 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 17574684 17574676 |
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| DOI: | 10.15252/emmm.202318028 |