CD20-Targeting Immunotherapy Promotes Cellular Senescence in B-Cell Lymphoma

Molecular Cancer Therapeutics
J Henry M DäbritzClemens A Schmitt

Abstract

The CD20-targeting monoclonal antibody rituximab is an established component of immunochemotherapeutic regimens against B-cell lymphomas, where its coadministration with conventional anticancer agents has significantly improved long-term outcome. However, the cellular mechanisms by which rituximab exerts its antilymphoma activity are only partially understood. We show here that rituximab induces typical features of cellular senescence, a long-term growth arrest of viable cells with distinct biologic properties, in established B-cell lymphoma cell lines as well as primary transformed B cells. In addition, rituximab-based immunotherapy sensitized lymphoma cells to senescence induction by the chemotherapeutic compound adriamycin (a.k.a. doxorubicin), and, to a lesser extent, by the antimicrotubule agent vincristine. Anti-CD20 treatment further enhanced secretion of senescence-associated cytokines, and augmented the DNA damage response signaling cascade triggered by adriamycin. As the underlying prosenescence mechanism, we found intracellular reactive oxygen species (ROS) levels to be elevated in response to rituximab, and, in turn, the ROS scavenger N-acetylcysteine to largely abrogate rituximab-mediated senescence. Our results, f...Continue Reading

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Citations

Mar 16, 2019·Immunological Reviews·Andrea BissoBruno Amati
Dec 1, 2017·Nature Reviews. Gastroenterology & Hepatology·Nina FreyMichael Bitzer
Dec 18, 2018·Current Drug Targets·Jieqiong YouBo Yang
Apr 3, 2020·Cancers·Tareq SalehDavid A Gewirtz
Mar 18, 2019·Biochemical Pharmacology·Yassin TachikartJean-Marc Brondello

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