解读焦点损伤瘤微环境中的中性粒细胞动态,以克服多发性骨髓瘤中的免疫抑制
Joshua Rivera1, Qi Yan2, Saeed Daneshmandi2
1Dana-Farber Cancer Institute and Harvard School of Public Health, Boston, Massachusetts, United States.
Blood
|August 4, 2025
概括
研究人员在多发性骨髓瘤 (MM) 骨髓和病变中确定了三个中性粒细胞子集. 一个子集抑制T细胞,与较短的存活率相关,表明CXCR2阻断作为治疗点.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 癌症研究 癌症研究
背景情况:
- 瘤微环境 (TME) 中的髓状细胞是克服多发性骨髓瘤 (MM) 免疫抑制的关键目标.
- 中性粒细胞越来越多地被认为是它们在调节免疫反应和潜在地阻碍抗癌疗法的作用.
研究的目的:
- 阐明中性粒细胞在MM瘤微环境中的功能性作用和表型.
- 确定特定的中性粒细胞子集,这些子集有助于免疫逃避和MM患者的不良预后.
主要方法:
- 来自MM焦点病变 (FL) 和骨髓 (BM) 的髓状细胞的单细胞RNA测序 (scRNA-seq).
- 免疫光成像和功能测试以表征中性粒细胞子集.
- 对大量MM患者数据集的分析,以将基因特征与整体存活率 (OS) 相关联.
- 临床前MM模型用于评估针对中性粒细胞活动的治疗策略.
主要成果:
- 鉴定了三个不同的CXCR2+成熟中性粒细胞子集:TREM1+CD10+,RETN+LCN2+和TNFAIP3+CXCL8+.
- 在FL中流行的TREM1+CD10+亚组对T细胞表现出显著的免疫抑制活性.
- 这一亚群的基因特征与MM患者的寿命缩短有关.
- 单独或与标准疗法一起阻断CXCR2,在临床前模型中减少瘤负担和改善OS.
结论:
- 中性粒细胞通过不同的子集功能在MM介导的免疫抑制中发挥着关键作用.
- TREM1+CD10+中性粒细胞子集代表了与MM的不良结果相关的临床显著因素.
- 通过CXCR2向中性粒细胞活性提供了一个有希望的治疗策略,以增强抗髓瘤免疫力和治疗疗效.
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