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单细胞转录基因地图的复发性巨细胞骨瘤后的新辅助性denosumab治疗

Xianglin Hu¹, Huajian Wu², Biqiang Zheng¹

¹Department of Musculoskeletal Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.

Journal of genetics and genomics = Yi chuan xue bao

|March 5, 2026

概括

针对骨巨细胞瘤 (GCTB) 的新辅助剂denosumab (DMAb) 可能通过改变瘤细胞并创造免疫抑制环境,增加复发风险. 向CSF1R和T细胞耗尽可能有助于管理复发的GCTB.

科学领域:

在瘤学瘤学.
免疫学免疫学免疫学
骨生物学骨生物学骨生物学

背景情况:

登诺苏马布 (DMAb) 是用于治疗骨巨细胞瘤 (GCTB) 的新辅助疗法.
有证据表明,新辅助剂DMAb可能会在切除后增加局部复发 (LR) 风险.
在GCTB中DMAb相关LR背后的机制尚未完全理解.

研究的目的:

研究GCTB中新辅助剂DMAb相关LR的细胞和分子机制.
确定复发性GCTB的潜在治疗点.

主要方法:

单细胞RNA测序在未经治疗,DMAb治疗和复发的GCTB样本上进行.
分析了细胞群,基因表达和免疫微环境.

主要成果:

新辅助剂DMAb减少了类似骨质细胞的巨细胞,但诱导了瘤细胞的转化.
德马治疗创造了一个免疫抑制瘤微环境,调节性T细胞 (Tregs) 增加,细胞毒性CD8+T细胞和自然杀伤性T细胞 (NKT) 减少.
单细胞分化成Trem2+巨细胞促进了瘤复发.

结论:

新辅助剂DMAb改变了GCTB细胞组成,并诱导了免疫抑制的微环境,可能增加LR风险.
向CSF1R和T细胞耗尽可能为在DMAb停止后复发的GCTB提供新的治疗策略.

关键词:

剪切的方法剪切的方法这就是Denosumab.骨巨细胞瘤的巨细胞瘤.当地复发局部复发核因子kappa-B连接体的受体激活剂.单细胞RNA测序的一个细胞.

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