CD20 expression regulates CD37 levels in B-cell lymphoma - implications for immunotherapies
| Autoři | |
|---|---|
| Rok publikování | 2024 |
| Druh | Článek v odborném periodiku |
| Časopis / Zdroj | Oncoimmunology |
| Fakulta / Pracoviště MU | |
| Citace | |
| www | https://www.tandfonline.com/doi/full/10.1080/2162402X.2024.2362454 |
| Doi | http://dx.doi.org/10.1080/2162402X.2024.2362454 |
| Klíčová slova | B-cell lymphoma; immunotherapy; rituximab; CD20; CD37; CAR T-cells |
| Přiložené soubory | |
| Popis | 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. |
| Související projekty: |