Browse by author
Lookup NU author(s): Professor Andrew GenneryORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
© 2022 by The American Society of Hematology. Anti-CD20 antibodies such as rituximab are broadly used to treat B-cell malignancies. These antibodies can induce various effector functions, including immune cell-mediated antibody-dependent cellular cytotoxicity (ADCC). Neutrophils can induce ADCC toward solid cancer cells by trogoptosis, a cytotoxic mechanism known to be dependent on trogocytosis. However, neutrophils seem to be incapable of killing rituximab-opsonized B-cell lymphoma cells. Nevertheless, neutrophils do trogocytose rituximab-opsonized B-cell lymphoma cells, but this only reduces CD20 surface expression and is thought to render tumor cells therapeutically resistant to further rituximab-dependent destruction. Here, we demonstrate that resistance of B-cell lymphoma cells toward neutrophil killing can be overcome by a combination of CD47-SIRPa checkpoint blockade and sodium stibogluconate (SSG), an anti-leishmaniasis drug and documented inhibitor of the tyrosine phosphatase SHP-1. SSG enhanced neutrophil-mediated ADCC of solid tumor cells but enabled trogoptotic killing of B-cell lymphoma cells by turning trogocytosis from a mechanism that contributes to resistance into a cytotoxic anti-cancer mechanism. Tumor cell killing in the presence of SSG required both antibody opsonization of the target cells and disruption of CD47-SIRPa interactions. These results provide a more detailed understanding of the role of neutrophil trogocytosis in antibody-mediated destruction of B cells and clues on how to further optimize antibody therapy of B-cell malignancies.
Author(s): van Rees DJ, Brinkhaus M, Klein B, Verkuijlen P, Tool ATJ, Schornagel K, Treffers LW, van Houdt M, Kater AP, Vidarsson G, Gennery AR, Kuijpers TW, van Bruggen R, Matlung HL, van den Berg TK
Publication type: Article
Publication status: Published
Journal: Blood Advances
Year: 2022
Volume: 6
Issue: 7
Pages: 2156-2166
Print publication date: 12/04/2022
Online publication date: 23/12/2021
Acceptance date: 17/11/2021
Date deposited: 10/05/2022
ISSN (print): 2473-9529
ISSN (electronic): 2473-9537
Publisher: American Society of Hematology
URL: https://doi.org/10.1182/bloodadvances.2021005367
DOI: 10.1182/bloodadvances.2021005367
PubMed id: 34942000
Altmetrics provided by Altmetric
