Sodium stibogluconate and CD47-SIRPα blockade overcome resistance of anti-CD20-opsonized B cells to neutrophil killing.

Autor:	van Rees DJ; Department of Molecular Hematology and., Brinkhaus M; Department of Experimental Immunohematology, Sanquin Research and Landsteiner Laboratory, Amsterdam, The Netherlands., Klein B; Department of Molecular Hematology and., Verkuijlen P; Department of Molecular Hematology and., Tool ATJ; Department of Molecular Hematology and., Schornagel K; Department of Molecular Hematology and., Treffers LW; Department of Molecular Hematology and., van Houdt M; Department of Molecular Hematology and., Kater AP; Department of Hematology, Cancer Center Amsterdam, Lymphoma and Myeloma Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., Vidarsson G; Department of Experimental Immunohematology, Sanquin Research and Landsteiner Laboratory, Amsterdam, The Netherlands., Gennery AR; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom., Kuijpers TW; Department of Molecular Hematology and.; Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; and., van Bruggen R; Department of Molecular Hematology and., Matlung HL; Department of Molecular Hematology and., van den Berg TK; Department of Molecular Hematology and.; Department of Molecular Cell Biology and Immunology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2022 Apr 12; Vol. 6 (7), pp. 2156-2166.
DOI:	10.1182/bloodadvances.2021005367
Abstrakt:	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-SIRPα 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-SIRPα 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. (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
Databáze:	MEDLINE
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