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在肝细胞癌中,XOR-IDH3α轴控制着巨分化

Yijun Lu¹, Qikai Sun², Qifei Guan¹

¹Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.

Journal of hepatology

|July 20, 2023

概括

在与瘤相关的巨细胞中,丁氧化还原酶 (XOR) 损失通过增强M2极化和CD8+T细胞耗尽,促进肝细胞癌 (HCC) 的进展. 准XOR-IDH3α轴可能为HCC提供新的免疫治疗策略.

科学领域:

免疫学免疫学免疫学
代谢途径代谢途径
癌症生物学癌症生物学

背景情况:

瘤相关巨细胞 (TAMs) 是肝细胞癌 (HCC) 瘤微环境中的关键参与者.
氨酸氧化还原酶 (XOR) 影响巨细胞的两极分化,但其在HCC TAMs中的作用尚不清楚.

研究的目的:

调查XOR在与HCC相关的TAM中的作用.
阐明XOR影响TAM极化和HCC进展的分子机制.

主要方法:

在HCC组织和配对的邻近组织中评估XOR水平.
建立由二甲基胺/四化碳 (CCl4) 诱导和正体植入的HCC小鼠模型,具有髓状细胞特异性或库弗弗细胞特异性Xdh枯竭.
代谢和代谢流量分析以确定代谢差异.

主要成果:

在HCC TAM中,XOR表达下调,与患者存活率较差相关.
单细胞衍生TAM中的XOR损失促进了M2极化和CD8+T细胞耗尽,加剧了HCC.
XOR 枯竭增强了 IDH3α 活性,导致α-甲酸酸盐,腺素和金酸的产生增加,促进免疫抑制.

结论:

XOR-IDH3α轴对TAM极化和HCC进展至关重要.
针对这一轴提出了针对免疫抑制性HCC TAMs的潜在治疗策略.

关键词:

与瘤相关的巨细胞.肝细胞癌是肝细胞癌.免疫疗法免疫疗法异酸盐脱酶3α是什么亚丁氧化降解酶 (xanthine oxidoreductase) 是一种可以减少亚酸的药物.

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