胶质母细胞瘤 IDH 野生型的肿瘤微环境具有高度免疫抑制性，其特征是髓源性抑制细胞 (MDSC) 的强大成分。为了干扰 MDSC 的免疫抑制功能，全面了解 MDSC 如何获得其抑制表型至关重要。此前，我们和其他人已经展示了胶质母细胞瘤中 MDSC 独特的唾液酸结合免疫球蛋白样凝集素 (Siglec) 受体表达谱。 Siglec 受体可以传递与 PD-1 相当的抑制信号，并被建议充当糖免疫检查点。在这里，我们研究了神经胶质瘤特异性 Siglec-唾液酸相互作用如何影响骨髓免疫抑制功能。将单核细胞与胶质母细胞瘤细胞共培养可诱导单核细胞表达 CD163。胶质母细胞瘤细胞去唾液酸化后，CD163 的诱导受到阻碍，此外，与完全唾液酸化的胶质母细胞瘤细胞相比，单核细胞现在能够分泌更高量的 IL-6 和 TNFα。此外，使用抗 Siglec-7 或 Siglec-9 抗体的 Siglec 特异性触发显示单核细胞的 TNFα 分泌减少，验证了 Siglec-Sialic 轴在共培养实验中的作用。总之，我们的结果表明，胶质母细胞瘤细胞诱导骨髓免疫抑制表型，可以通过降低胶质母细胞瘤相关唾液酸水平来部分挽救。本手稿支持在胶质母细胞瘤背景下进一步研究 Siglec-唾液酸轴及其改善临床结果的潜力。

The tumor microenvironment of glioblastoma IDH-wildtype is highly immune suppressive and is characterized by a strong component of myeloid-derived suppressor cells (MDSCs). To interfere with the immune suppressive functions of MDSCs, a comprehensive understanding on how MDSCs acquire their suppressive phenotype is essential. Previously, we and others have shown a distinct Sialic acid-binding immunoglobulin-like lectin (Siglec) receptor expression profile for MDSCs in glioblastoma. Siglec receptors can transmit inhibitory signals comparable to PD-1 and are suggested to act as glyco-immune checkpoints. Here, we investigated how glioma specific Siglec-sialic acid interactions influence myeloid immune suppressive functions. Co-culturing monocytes with glioblastoma cells induced CD163 expression on the monocytes. Upon desialylation of the glioblastoma cells, this induction of CD163 was hampered, and furthermore, the monocytes were now able to secrete higher amounts of IL-6 and TNFα compared to fully sialylated glioblastoma cells. Additionally, Siglec-specific triggering using anti-Siglec-7 or Siglec-9 antibodies displayed a decreased TNFα secretion by the monocytes, validating the role of the Siglec-Sialic axis in the co-culture experiments. Together, our results demonstrate that glioblastoma cells induce a myeloid immune-suppressive phenotype that could be partly rescued by lowering the glioblastoma-associated sialic acid levels. This manuscript supports further research of the Siglec-Sialic acid axis in the context of glioblastoma and its potential to improve clinical outcome.