Modulation of Siglec-7 Signaling Via In Situ-Created High-Affinity <i>cis</i>-Ligands
Senlian Hong, Chenhua Yu, Emily Rodrigues, Yujie Shi, Hongmin Chen, Peng Wang, Digantkumar Chapla, Tao Gao, Ruoxuan Zhuang, Kelley W. Moremen, James C. Paulson, Matthew S. Macauley, Peng Wu
Abstract
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.