%0 Journal Article
%T CD20 expression regulates CD37 levels in B-cell lymphoma - implications for immunotherapies.
%A Bobrowicz M
%A Kusowska A
%A Krawczyk M
%A Zhylko A
%A Forcados C
%A Slusarczyk A
%A Barankiewicz J
%A Domagala J
%A Kubacz M
%A Šmída M
%A Dostalova L
%A Marhelava K
%A Fidyt K
%A Pepek M
%A Baranowska I
%A Szumera-Cieckiewicz A
%A Inderberg EM
%A Wälchli S
%A Granica M
%A Graczyk-Jarzynka A
%A Majchrzak M
%A Poreba M
%A Gehlert CL
%A Peipp M
%A Firczuk M
%A Prochorec-Sobieszek M
%A Winiarska M
%J Oncoimmunology
%V 13
%N 1
%D 2024
%M 38846084
暂无%R 10.1080/2162402X.2024.2362454
%X 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.