Amsterdam UMC location Vrije Universiteit Amsterdam, Molecular Cell Biology and Immunology, Cancer Center Amsterdam, Amsterdam Institute for Infection and Immunity, De Boelelaan, 1117, Amsterdam, The Netherlands.
Amsterdam UMC location Vrije Universiteit Amsterdam, Molecular Cell Biology and Immunology, Cancer Center Amsterdam, Amsterdam Institute for Infection and Immunity, De Boelelaan, 1117, Amsterdam, The Netherlands.
Trends Cancer. 2024 Mar;10(3):230-241. doi: 10.1016/j.trecan.2023.11.009. Epub 2023 Dec 29.
Advances in immunotherapy have revolutionized cancer treatment, yet many patients do not show clinical responses. While most immunotherapies target T cells, myeloid cells are the most abundant cell type in solid tumors and are key orchestrators of the immunosuppressive tumor microenvironment (TME), hampering effective T cell responses. Therefore, unraveling the immune suppressive pathways within myeloid cells could unveil new avenues for cancer immunotherapy. Over the past decade, Siglec receptors and their ligand, sialic acids, have emerged as a novel immune checkpoint on myeloid cells. In this review, we highlight key findings on how sialic acids modify immunity in the TME through engagement of Siglec-7/9/10/15 expressed on myeloid cells, and how the sialic acid-Siglec axis can be targeted for future cancer immunotherapies.
免疫疗法的进步彻底改变了癌症治疗方式，但许多患者并未表现出临床反应。虽然大多数免疫疗法针对 T 细胞，但髓样细胞是实体瘤中最丰富的细胞类型，也是免疫抑制肿瘤微环境（TME）的关键协调者，阻碍了有效的 T 细胞反应。因此，揭示髓样细胞中的免疫抑制途径可能为癌症免疫疗法开辟新途径。在过去的十年中，Siglec 受体及其配体唾液酸已成为髓样细胞上的新型免疫检查点。在这篇综述中，我们强调了关键发现，即通过髓样细胞上表达的 Siglec-7/9/10/15 与唾液酸的结合，唾液酸如何调节 TME 中的免疫，以及如何针对唾液酸-Siglec 轴进行未来的癌症免疫治疗。
