Nature (2019)

CD24 is an inhibitory molecule with high expression on multiple tumor cell types, including ovarian and triple-negative breast cancers. In Nature, Barkal et al. show that the inhibitory receptor Siglec-10 expressed on tumor-associated macrophages suppresses their ability to phagocytose CD24+ tumor cells. The cytokines IL-10 and TGF-β induce Siglec-10 expression by tumor-associated macrophages. Disrupting the CD24–Siglec-10 interaction either by genetic loss of CD24 or SIGLEC10 or by monoclonal antibody–mediated blockade increases macrophage-dependent phagocytosis of tumor cells, which indicates that CD24–Siglec-10 binding provides a ‘don’t eat me’ signal. Combined blockade of CD24 and CD47 (another ‘don’t eat me’ molecule) synergistically enhances the ability of macrophages to phagocytize primary human tumor cells in vitro. Mouse macrophages also show enhanced phagocytosis of CD24-deficient tumor cells in vivo. These findings suggest that targeting CD24–Siglec-10 interactions might prove beneficial for immunotherapy in cancer.