SSG potentiates neutrophil ADCC and overcomes B-cell lymphoma cell resistance toward neutrophil killing. (A-B) Neutrophil ADCC and trogocytosis of wild type and Raji CD47KO cells opsonized with rituximab, obinutuzumab, or ofatumumab in the absence or presence of 100 µM SSG (n = 6-12 donors from 6 independent experiments for ADCC). There were no significant differences between control conditions and opsonized cells in absence of SSG (n = 6-10 donors from 5 independent experiments for trogocytosis). (C) Representative histograms of neutrophil DiD positivity (tumor cell membrane dye) in a trogocytosis experiment with Raji wild type or CD47KO cells opsonized with or without rituximab, in the absence or presence of SSG (dark gray–shaded histograms). (D) Neutrophil ADCC of Raji cells opsonized with or without rituximab in the absence or presence of SSG (purple bars). CD47-SIRPα signaling is inhibited by using Raji CD47KO cells or by blocking neutrophil SIRPα using SIRPα-blocking antibodies (n = 14 donors from 8 independent experiments). (E) Neutrophil ADCC of Raji wild type cells, Raji CD47KO cells, or Raji CD47KO cells with CD47 reconstitution, opsonized with or without rituximab in the absence or presence of SSG. The y-axis depicts the amount of cytotoxicity relative to the expression of CD47 on the Raji cells to highlight the role of CD47 on the tumor cells during ADCC by neutrophils (n = 6 donors from 3 independent experiments). (F) Representative histogram of the CD47 expression of Raji wild type cells, Raji CD47KO cells, or Raji CD47KO cells with CD47 reconstitution. Data are mean ± SEM. *P ≤ .05; **P ≤ .01; ***P ≤ .001; ****P ≤ .0001.