دورية أكاديمية
Rapid functional impairment of natural killer cells following tumor entry limits anti-tumor immunity
| العنوان: | Rapid functional impairment of natural killer cells following tumor entry limits anti-tumor immunity |
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| المؤلفون: | Dean, Isaac (University of Birmingham), Clatworthy, Menna R. (University of Cambridge / Wellcome Genome Campus), Baker, Syed Murtuza (University of Manchester), Lindforss, Ulrik (Karolinska University Hospital), Nordenvall, Caroline (Karolinska University Hospital), Fiancette, Rémi (University of Birmingham), Matei-Rascu, Veronika (University of Birmingham), Kennedy, Bethany C. (University of Birmingham), Gaspal, Fabrina (University of Birmingham), Willis, Claire (University of Birmingham), Tibbitt, Christopher A. (Karolinska Institutet), Li, Zhi (University of Birmingham), Withers, David R. (University of Birmingham), Lee, Colin Y. C. (University of Cambridge / Wellcome Genome Campus), Tuong, Zewen K. (University of Cambridge / Wellcome Genome Campus), Carlesso, Gianluca (AstraZeneca), Hepworth, Matthew R. (University of Manchester), Mjösberg, Jenny (Karolinska Institutet / Karolinska University Hospital), Dovedi, Simon J. (AstraZeneca), Hammond, Scott A. (AstraZeneca), Sexl, Veronika (University of Veterinary Medicine Vienna), Stockmann, Christian (University of Zurich) |
| المصدر: | Nature Communications 15(1) (2024) |
| بيانات النشر: | Nature Portfolio |
| سنة النشر: | 2024 |
| مصطلحات موضوعية: | Innate Lymphoid-Cells, Cd8(+) T-Cells, Mouse Nk Cells, Growth-Factor, Adaptive Immunity, Dendritic Cells, In-Vivo, Expression, Programs, Differentiation |
| الوصف: | Immune cell dysfunction within the tumor microenvironment (TME) undermines the control of cancer progression. Established tumors contain phenotypically distinct, tumor-specific natural killer (NK) cells; however, the temporal dynamics, mechanistic underpinning and functional significance of the NK cell compartment remains incompletely understood. Here, we use photo-labeling, combined with longitudinal transcriptomic and cellular analyses, to interrogate the fate of intratumoral NK cells. We reveal that NK cells rapidly lose effector functions and adopt a distinct phenotypic state with features associated with tissue residency. NK cell depletion from established tumors did not alter tumor growth, indicating that intratumoral NK cells cease to actively contribute to anti-tumor responses. IL-15 administration prevented loss of function and improved tumor control, generating intratumoral NK cells with both tissue-residency characteristics and enhanced effector function. Collectively, our data reveals the fate of NK cells after recruitment into tumors and provides insight into how their function may be revived. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | isPartOf:https://phaidra.vetmeduni.ac.at/o:605Test[Publications / University of Veterinary Medicine Vienna]; https://phaidra.vetmeduni.ac.at/o:3072Test |
| DOI: | 10.1038/s41467-024-44789-z |
| الإتاحة: | https://doi.org/10.1038/s41467-024-44789-zTest https://phaidra.vetmeduni.ac.at/o:3072Test |
| حقوق: | CC BY 4.0 International ; http://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.1E2790EA |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-024-44789-z |
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