{Reference Type}: Journal Article
{Title}: CD20 expression regulates CD37 levels in B-cell lymphoma - implications for immunotherapies.
{Author}: Bobrowicz M;Kusowska A;Krawczyk M;Zhylko A;Forcados C;Slusarczyk A;Barankiewicz J;Domagala J;Kubacz M;Šmída M;Dostalova L;Marhelava K;Fidyt K;Pepek M;Baranowska I;Szumera-Cieckiewicz A;Inderberg EM;Wälchli S;Granica M;Graczyk-Jarzynka A;Majchrzak M;Poreba M;Gehlert CL;Peipp M;Firczuk M;Prochorec-Sobieszek M;Winiarska M;
{Journal}: Oncoimmunology
{Volume}: 13
{Issue}: 1
{Year}: 2024
暂无{DOI}: 10.1080/2162402X.2024.2362454
{Abstract}: 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.