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通过B7-H3阻断增强T淋巴细胞介导的抗瘤免疫力,促进瘤血管正常化

Xin Dai¹, Boran Cao², Xinnan Liu³

¹Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China; Department of Oncology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.

European journal of pharmacology

|February 1, 2025

概括

B7-H3是三阴性乳腺癌 (TNBC) 的有希望的治疗标. 阻断B7-H3可能会改善免疫疗法反应和瘤血管正常化,特别是与PD-1抑制剂结合使用时.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
分子生物学分子生物学

背景情况:

三重阴性乳腺癌 (TNBC) 缺乏ER,PR和HER2,这给治疗带来了挑战,并且往往导致预后不佳.
免疫疗法耐药性是TNBC患者的一个子集的一个重要问题.
B7-H3,一个免疫检查点,与糟糕的结果有关,并在瘤血管系统中表达.

研究的目的:

研究B7-H3作为三阴性乳腺癌的治疗点.
在TNBC模型中评估单独或与抗PD-1疗法结合的抗B7-H3阻塞的疗效.

主要方法:

在TNBC患者组织中分析B7-H3表达.
使用TNBC小鼠模型进行体内研究,以评估抗B7-H3阻塞效应.
使用人类静脉内皮细胞 (HUVEC) 进行体外实验,研究B7-H3在淋巴细胞增殖和迁移中的作用.
研究了NF-κB信号通路.

主要成果:

在TNBC内皮细胞中观察到高B7-H3表达,与预后不佳相关.
在小鼠中,抗B7-H3阻塞降低了瘤负担,增强了淋巴细胞透,并使瘤血管正常化.
联合抗B7-H3和抗PD-1封锁显示出协同效应.
抗B7-H3通过NF-κB抑制抑制了HUVEC增殖,并促进了淋巴细胞迁移.

结论:

B7-H3是TNBC的一个潜在的治疗点.
与抗B7-H3和抗PD-1的联合治疗可能为TNBC治疗提供协同效益.

关键词:

B7-H3 B7-H3 B7-H3 B7-H3 B7-H3 B7-H3 B7-H3 B7-H3 B7-H3 B7-H3 B7-H3 B7-H3 淋巴细胞的透透.在PD-L1中.美国TNBC电视台瘤血管正常化瘤血管正常化

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