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

Fucosylation Promotes Cytolytic Function and Accumulation of NK Cells in B Cell Lymphoma.
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DOI:
10.3389/fimmu.2022.904693
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发表时间:
2022
影响因子:
7.3
通讯作者:
--
中科院分区:
医学2区
文献类型:
--
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自然杀伤 (NK) 细胞已被证明是一种有前途的细胞疗法,因为它们可以发挥有效的抗肿瘤免疫反应。然而,由于转移的NK细胞在体内的存活率较低且持续时间短,NK细胞在肿瘤免疫治疗中的应用,特别是在晚期造血系统和实体恶性肿瘤的治疗中的应用仍然受到限制。在这里,我们观察到岩藻糖基转移酶(FUT)7和8在NK细胞上高表达,并且CLA的表达与临床B细胞淋巴瘤发展中NK细胞的积累呈正相关。通过酶介导的离体细胞表面岩藻糖基化,NK 细胞对 B 细胞淋巴瘤的细胞溶解作用显着增强。岩藻糖基化还通过增强 NK 细胞与 E-选择素的结合,促进 B 细胞淋巴瘤靶组织中的 NK 细胞积累。此外,NK细胞的岩藻糖基化还促进了更强的T细胞抗肿瘤免疫反应。这些发现表明,离体岩藻糖基化有助于增强 NK 细胞的效应功能,并可能作为肿瘤免疫治疗的新策略。
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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