研究和靶向癌症中的 Siglec-唾液酸轴的工具,The FEBS Journal

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研究和靶向癌症中的 Siglec-唾液酸轴的工具
The FEBS Journal ( IF 5.5 ) Pub Date : 2020-11-29 , DOI: 10.1111/febs.15647
Heinz Läubli ₁ , Kunio Kawanishi ₂ , Cijo George Vazhappilly ₃ , Rachel Matar ₃ , Maxime Merheb ₃ , Shoib Sarwar Siddiqui ₃

Affiliation

Siglecs 在白细胞上广泛表达，并与普遍存在的含有唾液酸的聚糖（唾液酸聚糖）结合。大多数 Siglecs 携带基于免疫受体酪氨酸的抑制基序 (ITIM)，并在配体结合时引发抑制性细胞内信号。然而，一些 Siglec 受体可以募集免疫受体酪氨酸基激活基序 (ITAM) 因子，可激活细胞。最近研究了唾液酸化过度（唾液酸聚糖的表达增强）在癌症进展中的作用。机制研究表明，癌细胞上的过度唾液酸化可以与免疫细胞表面的抑制性 Siglecs 结合并诱导免疫抑制。这些最近的研究强烈表明 Siglec-唾液酸轴可以作为癌症免疫治疗的潜在靶点。此外，新工具和技术的使用正在促进这些研究。在这篇综述中，我们总结了用于研究 Siglecs 的技术，包括不同的小鼠模型、单克隆抗体、Siglec 融合蛋白和唾液聚糖阵列。此外，我们讨论了 Siglecs 在癌症免疫抑制、工具、

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Tools to study and target the Siglec–sialic acid axis in cancer

Siglecs are widely expressed on leucocytes and bind to ubiquitously presented glycans containing sialic acids (sialoglycans). Most Siglecs carry an immunoreceptor tyrosine-based inhibition motif (ITIM) and elicit an inhibitory intracellular signal upon ligand binding. A few Siglec receptors can, however, recruit immunoreceptor tyrosine-based activation motif (ITAM)-containing factors, which activate cells. The role of hypersialylation (the enhanced expression of sialoglycans) has recently been explored in cancer progression. Mechanistic studies have shown that hypersialylation on cancer cells can engage inhibitory Siglecs on the surface of immune cells and induce immunosuppression. These recent studies strongly suggest that the Siglec–sialic acid axis can act as a potential target for cancer immunotherapy. Moreover, the use of new tools and techniques is facilitating these studies. In this review, we summarise techniques used to study Siglecs, including different mouse models, monoclonal antibodies, Siglec fusion proteins, and sialoglycan arrays. Furthermore, we discuss the recent major developments in the study of Siglecs in cancer immunosuppression, tools, and techniques used in targeting the Siglec–sialic acid axis and the possibility of clinical intervention.

更新日期：2020-11-29

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