Galectin-9 是多种病理生理过程的多方面调节剂，以依赖于环境的方式发挥积极或消极的影响。在这里，我们阐明了 galectin-9 对脑肿瘤微环境中骨髓细胞的独特功能特性。在颅内小鼠脑肿瘤模型中，与对侧半球相比，荷瘤同侧半球的缺氧肿瘤边缘表达半乳糖凝集素 9 的细胞丰富。 Galectin-9 在肿瘤浸润细胞的小胶质细胞和巨噬细胞中高度表达。在原代胶质细胞中，半乳糖凝集素9的表达和分泌均受到肿瘤的影响。对人类胶质母细胞瘤批量 RNA 测序数据集和鼠神经胶质瘤模型的单细胞 RNA 测序数据集的分析揭示了 galectin-9 表达与神经胶质细胞激活之间的相关性。值得注意的是，脑肿瘤微环境中的 galectin-9high 小胶质细胞亚群在功能上不同于 galectin-9neg/low 亚群。 Galectin-9high 小胶质细胞表现出炎症激活和较高细胞死亡率的特性，而 Galectin-9neg/low 小胶质细胞则表现出对脑肿瘤细胞的卓越吞噬能力。阻断半乳糖凝集素 9 可抑制小鼠神经胶质瘤模型中的肿瘤生长并改变神经胶质细胞和 T 细胞的活性。此外，在缺氧脑肿瘤微环境中，胶质半乳糖凝集素 9 的表达受到 Hif-2α 的调节。骨髓特异性 Hif-2α 缺陷导致肿瘤进展减弱。总之，这些发现表明，骨髓细胞上的半乳糖凝集素 9 是脑肿瘤的免疫调节剂和假定的治疗靶点。

Galectin-9 is a multifaceted regulator of various pathophysiological processes that exerts positive or negative effects in a context-dependent manner. Here, we elucidated the distinctive functional properties of galectin-9 on myeloid cells within the brain tumor microenvironment. Galectin-9-expressing cells were abundant at the hypoxic tumor edge in the tumor-bearing ipsilateral hemisphere compared to the contralateral hemisphere in an intracranial mouse brain tumor model. Galectin-9 was highly expressed in microglia and macrophages in tumor-infiltrating cells. In primary glia, both the expression and secretion of galectin-9 were influenced by tumors. Analysis of a human glioblastoma bulk RNA-sequencing dataset and a single-cell RNA-sequencing dataset from a murine glioma model revealed a correlation between galectin-9 expression and glial cell activation. Notably, the galectin-9high microglial subset was functionally distinct from the galectin-9neg/low subset in the brain tumor microenvironment. Galectin-9high microglia exhibited properties of inflammatory activation and higher rates of cell death, whereas galectin-9neg/low microglia displayed a superior phagocytic ability against brain tumor cells. Blockade of galectin-9 suppressed tumor growth and altered the activity of glial and T cells in a mouse glioma model. Additionally, glial galectin-9 expression was regulated by Hif-2α in the hypoxic brain tumor microenvironment. Myeloid-specific Hif-2α deficiency led to attenuated tumor progression. Together, these findings reveal that galectin-9 on myeloid cells is an immunoregulator and putative therapeutic target in brain tumors.