التفاصيل البيبلوغرافية
| العنوان: |
RNF31 inhibition sensitizes tumors to bystander killing by innate and adaptive immune cells |
| المؤلفون: |
Zhang, Zhengkui, Kong, Xiangjun, Ligtenberg, Maarten A., van Hal-van Veen, Susan E., Visser, Nils L., de Bruijn, Beaunelle, Stecker, Kelly, van der Helm, Pim W., Kuilman, Thomas, Hoefsmit, Esmée P., Vredevoogd, David W., Apriamashvili, Georgi, Baars, Beau, Voest, Emile E., Klarenbeek, Sjoerd, Altelaar, Maarten, Peeper, Daniel S. |
| المساهمون: |
Externen Med. Onco, Cancer |
| سنة النشر: |
2022 |
| مصطلحات موضوعية: |
bystander killing, function-based genome-wide screens, immunotherapy resistance, NK cells, T cells, Tumor Escape, Ubiquitination, Killer Cells, Natural, Tumor Necrosis Factor-alpha/metabolism, Ubiquitin-Protein Ligases/genetics, General Biochemistry,Genetics and Molecular Biology, Research Support, Non-U.S. Gov't, Journal Article |
| الوصف: |
Tumor escape mechanisms for immunotherapy include deficiencies in antigen presentation, diminishing adaptive CD8+ T cell antitumor activity. Although innate natural killer (NK) cells are triggered by loss of MHC class I, their response is often inadequate. To increase tumor susceptibility to both innate and adaptive immune elimination, we performed parallel genome-wide CRISPR-Cas9 knockout screens under NK and CD8+ T cell pressure. We identify all components, RNF31, RBCK1, and SHARPIN, of the linear ubiquitination chain assembly complex (LUBAC). Genetic and pharmacologic ablation of RNF31, an E3 ubiquitin ligase, strongly sensitizes cancer cells to NK and CD8+ T cell killing. This occurs in a tumor necrosis factor (TNF)-dependent manner, causing loss of A20 and non-canonical IKK complexes from TNF receptor complex I. A small-molecule RNF31 inhibitor sensitizes colon carcinoma organoids to TNF and greatly enhances bystander killing of MHC antigen-deficient tumor cells. These results merit exploration of RNF31 inhibition as a clinical pharmacological opportunity for immunotherapy-refractory cancers. |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| تدمد: |
2666-3791 |
| العلاقة: |
https://dspace.library.uu.nl/handle/1874/448173Test |
| الإتاحة: |
https://dspace.library.uu.nl/handle/1874/448173Test |
| حقوق: |
info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: |
edsbas.DEF74F07 |
| قاعدة البيانات: |
BASE |
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