Sialylated CD43 forms a glyco-immune barrier that restrains antileukemic immunity

• 成果类型: Article
• 署名作者: Chung, Jooho; Vallurupalli, Mounica; Noel, Sarah; Schor, Gail; Mrowka, Sofia; Scapozza, Ilario; Demere, Zelalem; Kammula, Sachin V.; Hu, Margaret; Kim, Sarah Y.; Liu, YuhJong; Nobrega, Celeste; Perera, Jonathan J.; Wrona, Ewa; Cheruiyot, Collins K.; Lin, Yunkang; Wu, David W.; Saberi, Maria; Cruickshank, Aidan; Woods, Elliot C.; Chuong, Cun Lan; Birocchi, Filippo; Kammula, Ashwin V.; Avila, Omar I.; Knudsen, Nelson; Kocak, Mustafa; Doench, John G.; Procter, Dean; Thornton, Lindsey; Brunner, Andrew M.; Winer, Eric; DeAngelo, Daniel J.; Garcia, Jacqueline S.; Stone, Richard M.; Jenkins, Russell W.; Maus, Marcela V.; Graubert, Timothy A.; Yates, Kathleen B.; Golub, Todd R.; Manguso, Robert T.
• 署名单位: Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Medical University Lodz; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Dana-Farber Cancer Institute
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8075; 1095-9203
• DOI: 10.1126/science.ady5196
• 发表日期: 2026-04-09
• 页码: eady5196
• 关键词: mhc class-i; inhibitory receptor; MAJOR SIALOGLYCOPROTEIN; cutting edge; SIALIC ACIDS; macrophages; molecules; target; cells; mouse

摘要

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.