التفاصيل البيبلوغرافية
| العنوان: |
Multimodal stimulation screens reveal unique and shared genes limiting T cell fitness |
| المؤلفون: |
Lin, Chun Pu, Levy, Pierre L., Alflen, Astrid, Apriamashvili, Georgi, Ligtenberg, Maarten A., Vredevoogd, David W., Bleijerveld, Onno B., Alkan, Ferhat, Malka, Yuval, Hoekman, Liesbeth, Markovits, Ettai, George, Austin, Traets, Joleen J.H., Krijgsman, Oscar, van Vliet, Alex, Poźniak, Joanna, Pulido-Vicuña, Carlos Ariel, de Bruijn, Beaunelle, van Hal-van Veen, Susan E., Boshuizen, Julia, van der Helm, Pim W., Díaz-Gómez, Judit, Warda, Hamdy, Behrens, Leonie M., Mardesic, Paula, Dehni, Bilal, Visser, Nils L., Marine, Jean Christophe, Markel, Gal, Faller, William J., Altelaar, Maarten, Agami, Reuven, Besser, Michal J., Peeper, Daniel S. |
| المساهمون: |
Sub Biomol.Mass Spect. and Proteomics, Afd Biomol.Mass Spect. and Proteomics, Biomolecular Mass Spectrometry and Proteomics |
| سنة النشر: |
2024 |
| مصطلحات موضوعية: |
activation-induced cell death, cancer immunotherapy, CRISPR-Cas9 screen, Ctbp1, Dap5, dysfunction, effector function, exhaustion, Icam1, T cells, Oncology, Cancer Research |
| الوصف: |
Genes limiting T cell antitumor activity may serve as therapeutic targets. It has not been systematically studied whether there are regulators that uniquely or broadly contribute to T cell fitness. We perform genome-scale CRISPR-Cas9 knockout screens in primary CD8 T cells to uncover genes negatively impacting fitness upon three modes of stimulation: (1) intense, triggering activation-induced cell death (AICD); (2) acute, triggering expansion; (3) chronic, causing dysfunction. Besides established regulators, we uncover genes controlling T cell fitness either specifically or commonly upon differential stimulation. Dap5 ablation, ranking highly in all three screens, increases translation while enhancing tumor killing. Loss of Icam1-mediated homotypic T cell clustering amplifies cell expansion and effector functions after both acute and intense stimulation. Lastly, Ctbp1 inactivation induces functional T cell persistence exclusively upon chronic stimulation. Our results functionally annotate fitness regulators based on their unique or shared contribution to traits limiting T cell antitumor activity. |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| تدمد: |
1535-6108 |
| العلاقة: |
https://dspace.library.uu.nl/handle/1874/438097Test |
| الإتاحة: |
https://dspace.library.uu.nl/handle/1874/438097Test |
| حقوق: |
info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: |
edsbas.F4FB10B7 |
| قاعدة البيانات: |
BASE |
