National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China.
Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
Front Immunol. 2022 Jun 15;13:904693. doi: 10.3389/fimmu.2022.904693. eCollection 2022.
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 . 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. enzyme-mediated 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 fucosylation contributes to enhancing the effector functions of NK cells and may serve as a novel strategy for tumor immunotherapy.
自然杀伤 (NK) 细胞已被证明是一种很有前途的细胞疗法，因为它们能发挥强大的抗肿瘤免疫反应。然而，NK 细胞在肿瘤免疫治疗中的应用，特别是在治疗晚期血液系统和实体恶性肿瘤方面，仍然受到限制，因为转输的 NK 细胞的生存能力和持久性受到损害。在这里，我们观察到岩藻糖基转移酶 (FUT) 7 和 8 在 NK 细胞上高度表达，CLA 的表达与 NK 细胞在临床 B 细胞淋巴瘤发展中的积累呈正相关。通过酶介导的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著增强。岩藻糖基化还通过增强 NK 细胞与 E-选择素的结合，促进 NK 细胞在 B 细胞淋巴瘤靶向组织中的积累。此外，NK 细胞的岩藻糖基化也促进了更强的 T 细胞抗肿瘤免疫反应。这些发现表明，岩藻糖基化有助于增强 NK 细胞的效应功能，可能成为肿瘤免疫治疗的一种新策略。
