Fig. 7: T-DXd mediated immune activation is restricted by tumor CD47 expression. | Nature Communications

Fig. 7: T-DXd mediated immune activation is restricted by tumor CD47 expression.

From: Effective extracellular payload release and immunomodulatory interactions govern the therapeutic effect of trastuzumab deruxtecan (T-DXd)

Fig. 7

a Flow cytometry assessment of surface CD47 expression on Au565 cells after 2 days of treatment with DXd or DM1. b ADCP assessment of parental or CD47-KO KPL4 cells by human macrophages after 4 h co-culture. The percentage of macrophages containing fluorescent-labeled KPL4 was assessed by flow cytometry. c–i Human macrophages co-culture with indicated KPL4 target cells and treatments for 2 days. Macrophage surface expression of c HLA-A2, d HLA-DR, e CD80, and f CD40 were assessed by flow cytometry. Inflammatory cytokines g TNFα, h IL-6, and chemokine (i) CCL4 secreted by macrophages assessed by ELISA. n Tumor antigen (eGFP) presentation to JEDI CD8 T cells using BMDM co-cultured with treated KPL4-eGFP or KPL4-eGFP-CD47-KO cells. Representative flow graphs for JEDI T-cell proliferation assessment by Cell-Trace (j) or T-cell activation assessment by CD44 staining (l) are shown for each treatment condition. k JEDI T-cell proliferation summary and m CD44 expression summary. a–m Two-way ANOVA with Tukey’s or Šidák’s multiple comparisons test (n = 3 per group in all experiments). Data presented as mean ± SEM with p values. MFI mean fluorescence intensity.

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