气候变化领域集成服务门户(CCPortal): Genome-wide CRISPR screens reveal a specific ligand for the glycan-binding immune checkpoint receptor Siglec-7

CCPortal

DOI	10.1073/pnas.2015024118
	Genome-wide CRISPR screens reveal a specific ligand for the glycan-binding immune checkpoint receptor Siglec-7
	Wisnovsky S.; Möckl L.; Malaker S.A.; Pedram K.; Hess G.T.; Riley N.M.; Gray M.A.; Smith B.A.H.; Bassik M.C.; Moerner W.E.; Bertozzi C.R.
发表日期	2021
ISSN	00278424
卷号	118 期号:5
英文摘要	Glyco-immune checkpoint receptors, molecules that inhibit immune cell activity following binding to glycosylated cell-surface antigens, are emerging as attractive targets for cancer immunotherapy. Defining biologically relevant ligands that bind and activate such receptors, however, has historically been a significant challenge. Here, we present a CRISPRi genomic screening strategy that allowed unbiased identification of the key genes required for cell-surface presentation of glycan ligands on leukemia cells that bind the glyco-immune checkpoint receptors Siglec-7 and Siglec-9. This approach revealed a selective interaction between Siglec-7 and the mucin-type glycoprotein CD43. Further work identified a specific N-terminal glycopeptide region of CD43 containing clusters of disialylated O-glycan tetrasaccharides that form specific Siglec-7 binding motifs. Knockout or blockade of CD43 in leukemia cells relieves Siglec-7-mediated inhibition of immune killing activity. This work identifies a potential target for immune checkpoint blockade therapy and represents a generalizable approach to dissection of glycan–receptor interactions in living cells. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	CRISPR Screening; Glycobiology; Tumor Immunology
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180816
作者单位	Department of Chemistry &, Stanford ChEM-H, Stanford University, Stanford, CA 94305, United States; Max Planck Institute for the Science of Light, Erlangen, 91058, Germany; Department of Genetics, Stanford University, Stanford, CA 94305, United States; Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305, United States; Howard Hughes Medical Institute, Stanford, CA 94305, United States
推荐引用方式 GB/T 7714	Wisnovsky S.,Möckl L.,Malaker S.A.,et al. Genome-wide CRISPR screens reveal a specific ligand for the glycan-binding immune checkpoint receptor Siglec-7[J],2021,118(5).
APA	Wisnovsky S..,Möckl L..,Malaker S.A..,Pedram K..,Hess G.T..,...&Bertozzi C.R..(2021).Genome-wide CRISPR screens reveal a specific ligand for the glycan-binding immune checkpoint receptor Siglec-7.Proceedings of the National Academy of Sciences of the United States of America,118(5).
MLA	Wisnovsky S.,et al."Genome-wide CRISPR screens reveal a specific ligand for the glycan-binding immune checkpoint receptor Siglec-7".Proceedings of the National Academy of Sciences of the United States of America 118.5(2021).