Academic Journal
CD20 expression regulates CD37 levels in B-cell lymphoma - implications for immunotherapies
| العنوان: | CD20 expression regulates CD37 levels in B-cell lymphoma - implications for immunotherapies |
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| المؤلفون: | Bobrowicz Malgorzata, Kusowska Aleksandra, Krawczyk Marta, Zhylko Andriy, Forcados Christopher, Slusarczyk Aleksander, Barankiewicz Joanna, Domagala Joanna, Kubacz Matylda, Šmída Michal, Dostalová Kopečná Lenka, Marhelava Katsiaryna, Fidyt Klaudyna, Pepek Monika, Baranowska Iwona, Szumera-Cieckiewicz Anna, Inderberg Else Marit, Walchli Sebastien, Granica Monika, Graczyk-Jarzynka Agnieszka, Majchrzak Martyna, Poreba Marcin, Gehlert Carina Lynn, Peipp Matthias, Firczuk Malgorzata, Prochorec-Sobieszek Monika, Winiarska Magdalena |
| المصدر: | Oncoimmunology |
| بيانات النشر: | Taylor & Francis |
| سنة النشر: | 2024 |
| المجموعة: | Masaryk University: Open Services of Information System / Masarykova univerzita: Veřejné služby Informačního systému |
| مصطلحات موضوعية: | B-cell lymphoma, immunotherapy, rituximab, CD20, CD37, CAR T-cells |
| الوصف: | Rituximab (RTX) plus chemotherapy (R-CHOP) applied as a first-line therapy for lymphoma leads to a relapse in approximately 40% of the patients. Therefore, novel approaches to treat aggressive lymphomas are being intensively investigated. Several RTX-resistant (RR) cell lines have been established as surrogate models to study resistance to R-CHOP. Our study reveals that RR cells are characterized by a major downregulation of CD37, a molecule currently explored as a target for immunotherapy. Using CD20 knockout (KO) cell lines, we demonstrate that CD20 and CD37 form a complex, and hypothesize that the presence of CD20 stabilizes CD37 in the cell membrane. Consequently, we observe a diminished cytotoxicity of anti-CD37 monoclonal antibody (mAb) in complement-dependent cytotoxicity in both RR and CD20 KO cells that can be partially restored upon lysosome inhibition. On the other hand, the internalization rate of anti-CD37 mAb in CD20 KO cells is increased when compared to controls, suggesting unhampered efficacy of antibody drug conjugates (ADCs). Importantly, even a major downregulation in CD37 levels does not hamper the efficacy of CD37-directed chimeric antigen receptor (CAR) T cells. In summary, we present here a novel mechanism of CD37 regulation with further implications for the use of anti-CD37 immunotherapies. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | https://is.muni.cz/publication/2414117 |
| DOI: | 10.1080/2162402X.2024.2362454 |
| الاتاحة: | https://is.muni.cz/publication/2414117 https://doi.org/10.1080/2162402X.2024.2362454 |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.FC85B8C0 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1080/2162402X.2024.2362454 |
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