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在清细胞细胞癌中,SPP1+瘤相关的巨细胞通过CD8+T细胞功能障碍驱动免疫疗法抵抗

Wenbin Jiang¹, Li Liu², Ziyang Xu²

¹Zhongshan Hospital, Fudan University, Shanghai, China.

Cancer immunology research

|July 18, 2025

概括

在清细胞细胞癌 (ccRCC) 中,高水平的SPP1+TAM与免疫治疗反应和预后不佳相关. 向SPP1显示出有希望的 CD8+ T 细胞的再生和增强抗瘤免疫力.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
细胞癌研究细胞癌研究

背景情况:

瘤相关巨细胞 (TAMs),特别是SPP1+TAMs,是各种癌症中瘤免疫的公认调节者.
在清细胞细胞癌 (ccRCC) 中SPP1+TAMs的特定作用和临床意义仍未得到充分研究.

研究的目的:

研究ccRCC中SPP1+TAMs的临床相关性和表型特征.
在ccRCC中探索SPP1+TAM透,治疗反应和患者预后之间的关系.
评估针对ccRCC中的SPP1的治疗潜力.

主要方法:

来自内部 (n=355) 和公共 (n=1,741) ccRCC队列的患者级数据的分析.
用CyTOF和流式细胞计量对SPP1+TAMs的表型化和对它们对CD8+T细胞的影响的评估.
建立一个ex vivo培养系统来测试SPP1和PD-1阻塞策略.

主要成果:

在ccRCC中高SPP1+TAM透与免疫治疗反应减弱和预后较差有关.
SPP1+ TAMs表现出一种免疫抑制的表型,损害了CD8+ T细胞的功能和分化.
单独或与PD-1阻断相结合的SPP1阻断显示出改善瘤微环境和增强抗瘤CD8+T细胞反应的潜力.

结论:

在ccRCC中SPP1+TAM升高表明预后较差,CD8+T细胞免疫力受损.
在ccRCC中,SPP1代表了改善免疫治疗结果的潜在治疗标.
对SPP1和PD-1的联合向可能在ccRCC中提供增强的抗瘤疗效.

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