Sialylated CD43 forms a glyco-immune barrier that restrains antileukemic immunity
Summary
Macrophages exert antitumorigenic activity through phagocytosis, but phagocytosis-enhancing therapeutics have not improved acute myeloid leukemia (AML) outcomes. To identify phagocytosis regulators, we performed CRISPR knockout screens in human AML cells cocultured with human macrophages. We found that the "don't eat me" signal CD47 inhibited mouse but not human macrophage phagocytosis. However, O-linked glycosylation and sialylation were strong negative regulators of phagocytosis. In AML,
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# Sialylated CD43 forms a glyco-immune barrier that restrains antileukemic immunity
*Published: 2026 Apr 9*
Macrophages exert antitumorigenic activity through phagocytosis, but
phagocytosis-enhancing therapeutics have not improved acute myeloid leukemia
(AML) outcomes. To identify phagocytosis regulators, we performed CRISPR
knockout screens in human AML cells cocultured with human macrophages. We found
that the "don't eat me" signal CD47 inhibited mouse but not human macrophage
phagocytosis. However, O-linked glycosylation and sialylation were strong
negative regulators of phagocytosis. In AML, the cell surface mucin-like
glycoprotein CD43 was the major effector of these pathways. Inhibition of
phagocytosis by CD43 was dependent on the length of its ectodomain and
independent of the macrophage sialic acid receptors SIGLEC-1, SIGLEC-7, and
SIGLEC-9. The inhibitory effects of CD43 extended beyond human macrophages to
natural killer and T cells. Thus, CD43 forms a glyco-immune barrier that
restrains both innate and adaptive antileukemic immunity.
DOI: 10.1126/science.ady5196