与瘤相关的NK细胞通过IL-6/STAT3轴驱动MDSC介导的瘤免疫耐受性
Shi Yong Neo1,2, Le Tong1, Joni Chong2
1Department of Oncology-Pathology, Karolinska Institutet, 17164 Stockholm, Sweden.
Science translational medicine
|May 15, 2024
概括
自然杀手 (NK) 细胞在癌症中促进髓质衍生抑制细胞 (MDSCs) 的发展. 抑制IL-6/STAT3通路通过恢复T细胞功能来减少瘤生长.
科学领域:
- 免疫学 免疫学 免疫学
- 癌症生物学 癌症生物学
- 瘤微环境 瘤微环境
背景情况:
- 自然杀手 (NK) 细胞是重要的免疫细胞,其作用超出了细胞毒性,影响瘤微环境.
- 在免疫检查点疗法不响应者中,NK细胞和髓质衍生抑制细胞 (MDSC) 之间的相互作用尚不清楚.
研究的目的:
- 为了研究NK细胞和抑制性髓状细胞之间的交叉对话.
- 阐明NK细胞影响MDSC发育和功能的机制.
主要方法:
- 免疫基因解卷以确定细胞相互作用.
- 与NK细胞,单细胞和中性粒细胞进行共同培养实验.
- 分析与MDSC相关的抑制因素和免疫细胞功能.
- 患者队列研究 (肉瘤和乳腺癌) 和小鼠模型 (b2m-KO和IL-6 KO).
- 对IL-6/STAT3信号通路的评估.
主要成果:
- 经历瘤的NK细胞在单细胞和中性粒细胞中诱导了抑制性表型,增强了MDSC特征.
- NK细胞衍生IL-6与MDSC标记物 (S100A8/9,阿尔金酶-1) 和瘤中MHC I类表达相关.
- 在小鼠模型中,MDSC积累依赖于调节性NK细胞.
- 抑制IL-6/STAT3轴逆转T细胞抑制,减少瘤生长,并减少转移性传播.
结论:
- NK细胞通过IL-6的产生在推动MDSC发育中发挥着关键作用,有助于瘤免疫逃生.
- 准IL-6/STAT3通路是克服癌症NK细胞介导免疫抑制的潜在治疗策略.
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