L-fucose, a sugary regulator of antitumor immunity and immunotherapies.
L-fucose, a sugary regulator of antitumor immunity and immunotherapies.
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DOI：
10.1002/mc.23394
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发表时间：
2022-05
影响因子：
4.6
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中科院分区：
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L-岩藻糖是一种膳食糖，细胞在称为岩藻糖化的过程中使用这种糖来在翻译后修改和调节蛋白质的行为和功能。由于岩藻糖基化在正常器官和免疫发育和内稳态中发挥着重要的细胞功能，因此它被发现在包括癌症在内的许多病理生理环境中受到干扰也就不足为奇了。多年来，越来越多的研究强调了改变的岩藻糖基化在癌细胞内在以及旁分泌信号和相互作用中所起的关键作用。特别是，研究表明，岩藻糖基化影响肿瘤：免疫相互作用，并显著增强或减弱抗肿瘤免疫。重要的是，岩藻糖化似乎是一种翻译后修饰，可以作为治疗靶点，因为操纵岩藻糖化的分子基础已被证明足以损害或阻止肿瘤进展，并调节抗肿瘤免疫。此外，抗癌药物的岩藻糖基化，如治疗性抗体，已被证明对其疗效有重要影响。在这篇综述中，我们总结了岩藻糖化在肿瘤和免疫细胞中的作用，以及治疗性抗体的岩藻糖化或岩藻糖化的操作，以及它们作为癌症新的治疗手段的意义。
l-fucose is a dietary sugar that is used by cells in a process called fucosylation to post-translationally modify and regulate protein behavior and function. As fucosylation plays essential cellular functions in normal organ and immune developmental and homeostasis, it is perhaps not surprising that it has been found to be perturbed in a number of pathophysiological contexts, including cancer. Increasing studies over the years have highlighted key roles that altered fucosylation can play in cancer cell-intrinsic as well as paracrine signaling and interactions. In particular, studies have demonstrated that fucosylation impact tumor:immunological interactions and significantly enhance or attenuate antitumor immunity. Importantly, fucosylation appears to be a posttranslational modification that can be therapeutically targeted, as manipulating the molecular underpinnings of fucosylation has been shown to be sufficient to impair or block tumor progression and to modulate antitumor immunity. Moreover, the fucosylation of anticancer agents, such as therapeutic antibodies, has been shown to critically impact their efficacy. In this review, we summarize the underappreciated roles that fucosylation plays in cancer and immune cells, as well as the fucosylation of therapeutic antibodies or the manipulation of fucosylation and their implications as new therapeutic modalities for cancer.