Fucosylation Promotes Cytolytic Function and Accumulation of NK Cells in B Cell Lymphoma

岩藻糖基化促进 B 细胞淋巴瘤中的细胞溶解功能和 NK 细胞的积累

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作者:Xing Tong, Yuhua Ru, Jianhong Fu, Ying Wang, Jinjin Zhu, Yiyang Ding, Fulian Lv, Menglu Yang, Xiya Wei, Chenchen Liu, Xin Liu, Lei Lei, Xiaojin Wu, Lingchuan Guo, Yang Xu, Jie Li, Peng Wu, Huanle Gong, Jia Chen, Depei Wu

Abstract

Natural killer (NK) cells have been demonstrated as a promising cellular therapy as they exert potent anti-tumor immune responses. However, applications of NK cells to tumor immunotherapy, especially in the treatment of advanced hematopoietic and solid malignancies, are still limited due to the compromised survival and short persistence of the transferred NK cells in vivo. Here, we observed that fucosyltransferase (FUT) 7 and 8 were highly expressed on NK cells, and the expression of CLA was positively correlated with the accumulation of NK cells in clinical B cell lymphoma development. Via enzyme-mediated ex vivo cell-surface fucosylation, the cytolytic effect of NK cells against B cell lymphoma was significantly augmented. Fucosylation also promoted NK cell accumulation in B cell lymphoma-targeted tissues by enhancing their binding to E-selectin. Moreover, fucosylation of NK cells also facilitated stronger T cell anti-tumor immune responses. These findings suggest that ex vivo fucosylation contributes to enhancing the effector functions of NK cells and may serve as a novel strategy for tumor immunotherapy.

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