Department of Clinical Pharmacology, Medical University of Bialystok, Waszyngtona 15A, 15-274 Bialystok, Poland.
Department of Clinical Genetics, Medical University of Bialystok, Waszyngtona 13, 15-089 Bialystok, Poland.
Int J Mol Sci. 2021 Feb 11;22(4):1791. doi: 10.3390/ijms22041791.
The paired sialic acid-binding immunoglobulin like lectins (Siglecs) are characterized by similar cellular distribution and ligand recognition but opposing signalling functions attributed to different intracellular sequences. Since sialic acid-Siglec axis are known to control immune homeostasis, the imbalance between activatory and inhibitory mechanisms of glycan-dependent immune control is considered to promote pathology. The role of sialylation in cancer is described, however, its importance in immune regulation in gliomas is not fully understood. The experimental and clinical observation suggest that dexamethasone (Dex) and temozolomide (TMZ), used in the glioma management, alter the immunity within the tumour microenvironment. Using glioma-microglia/monocytes transwell co-cultures, we investigated modulatory action of Dex/TMZ on paired Siglecs. Based on real-time PCR and flow cytometry, we found changes in SIGLEC genes and their products. These effects were accompanied by altered cytokine profile and immune cells phenotype switching measured by arginases expression. Additionally, the exposure to Dex or TMZ increased the binding of inhibitory Siglec-5 and Siglec-11 fusion proteins to glioma cells. Our study suggests that the therapy-induced modulation of the interplay between sialoglycans and paired Siglecs, dependently on patient's phenotype, is of particular signification in the immune surveillance in the glioma management and may be useful in glioma patient's therapy plan verification.
配对唾液酸结合免疫球蛋白样凝集素（Siglecs）的特征在于相似的细胞分布和配体识别，但由于不同的细胞内序列而具有相反的信号功能。由于已知唾液酸-Siglec 轴控制免疫稳态，糖依赖性免疫控制的激活和抑制机制之间的失衡被认为可促进病理学。已经描述了唾液酸化在癌症中的作用，然而，其在神经胶质瘤免疫调节中的重要性尚未完全理解。实验和临床观察表明，用于神经胶质瘤管理的地塞米松（Dex）和替莫唑胺（TMZ）改变肿瘤微环境中的免疫。使用神经胶质瘤-小胶质细胞/单核细胞 Transwell 共培养物，我们研究了 Dex/TMZ 对配对 Siglecs 的调节作用。基于实时 PCR 和流式细胞术，我们发现了 SIGLEC 基因及其产物的变化。这些作用伴随着通过精氨酸酶表达测量的细胞因子谱和免疫细胞表型转换的改变。此外，暴露于 Dex 或 TMZ 增加了抑制性 Siglec-5 和 Siglec-11 融合蛋白与神经胶质瘤细胞的结合。我们的研究表明，治疗诱导的唾液糖和配对 Siglecs 之间相互作用的调节，取决于患者的表型，在神经胶质瘤管理中的免疫监视中具有特殊意义，并且可能对神经胶质瘤患者的治疗计划验证有用。
