Modulation of Siglec-7 Signaling Via In Situ-Created High-Affinity cis -Ligands.

Autor:	Hong S; State Key Laboratory of Natural and Biomimetic Drugs, Chemical Biology Center, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.; State Key Laboratory of Natural and Biomimetic Drugs, Chemical Biology Center, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.; State Key Laboratory of Natural and Biomimetic Drugs, Chemical Biology Center, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China., Yu C; Department of Molecular Medicine, Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla 92037, California, United States.; Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin 300060, China., Rodrigues E; Department of Chemistry, Department of Medical Microbiology and Immunology, University of Alberta, 11227 Saskatchewan Drive NW, Edmonton AB T6G 2G2, Alberta, Canada., Shi Y; Department of Molecular Medicine, Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla 92037, California, United States., Chen H; State Key Laboratory of Natural and Biomimetic Drugs, Chemical Biology Center, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China., Wang P; Department of Molecular Medicine, Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla 92037, California, United States., Chapla DG; Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia 30602, United States., Gao T; State Key Laboratory of Natural and Biomimetic Drugs, Chemical Biology Center, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China., Zhuang R; State Key Laboratory of Natural and Biomimetic Drugs, Chemical Biology Center, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China., Moremen KW; Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia 30602, United States., Paulson JC; Department of Molecular Medicine, Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla 92037, California, United States., Macauley MS; Department of Chemistry, Department of Medical Microbiology and Immunology, University of Alberta, 11227 Saskatchewan Drive NW, Edmonton AB T6G 2G2, Alberta, Canada.; Department of Chemistry, Department of Medical Microbiology and Immunology, University of Alberta, 11227 Saskatchewan Drive NW, Edmonton AB T6G 2G2, Alberta, Canada., Wu P; Department of Molecular Medicine, Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla 92037, California, United States.
Jazyk:	angličtina
Zdroj:	ACS central science [ACS Cent Sci] 2021 Aug 25; Vol. 7 (8), pp. 1338-1346. Date of Electronic Publication: 2021 Aug 13.
DOI:	10.1021/acscentsci.1c00064
Abstrakt:	Sialic acid-binding immunoglobulin-like lectins, also known as Siglecs, have recently been designated as glyco-immune checkpoints. Through their interactions with sialylated glycan ligands overexpressed on tumor cells, inhibitory Siglecs on innate and adaptive immune cells modulate signaling cascades to restrain anti-tumor immune responses. However, the elucidation of the mechanisms underlying these processes is just beginning. We find that when human natural killer (NK) cells attack tumor cells, glycan remodeling occurs on the target cells at the immunological synapse. This remodeling occurs through both the transfer of sialylated glycans from NK cells to target tumor cells and the accumulation of de novo synthesized sialosides on the tumor cells. The functionalization of NK cells with a high-affinity ligand of Siglec-7 leads to multifaceted consequences in modulating a Siglec-7-regulated NK-activation. At high levels of ligand, an enzymatically added Siglec-7 ligand suppresses NK cytotoxicity through the recruitment of Siglec-7 to an immune synapse, whereas at low levels of ligand an enzymatically added Siglec-7 ligand triggers the release of Siglec-7 from the cell surface into the culture medium, preventing a Siglec-7-mediated inhibition of NK cytotoxicity. These results suggest that a glycan engineering of NK cells may provide a means to boost NK effector functions for related applications. Competing Interests: The authors declare no competing financial interest. (© 2021 The Authors. Published by American Chemical Society.)
Databáze:	MEDLINE
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