通过传统的T细胞获得抑制功能,在Treg耗尽后限制了抗瘤免疫力
Sarah K Whiteside1, Francis M Grant2, Giorgia Alvisi3
1Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK.
Science immunology
|December 15, 2023
概括
削减与癌症作斗争的调节性T (Treg) 细胞可能会反作用. 传统的T (Tconv) 细胞获得抑制能力,阻碍治疗. 将IL-10信号与Treg耗尽一起定位可能改善癌症免疫疗法.
科学领域:
- 免疫学 免疫学 免疫学
- 癌症生物学 癌症生物学
- 免疫治疗是一种免疫疗法.
背景情况:
- 调节性T (Treg) 细胞维持免疫平衡,但抑制抗癌免疫反应.
- 目前针对Treg细胞的癌症免疫疗法由于对抗性机制的了解不足,其成功程度有限.
研究的目的:
- 调查Treg细胞向癌症免疫疗法的治疗失败背后的机制.
- 为了确定在Treg细胞枯竭时激活的替代性免疫抑制途径.
主要方法:
- 对Treg细胞向免疫疗法的小鼠模型.
- 分析T细胞种群,基因表达 (转录概况) 和抑制功能ex vivo.
- 评估IL-10在免疫抑制和治疗功效中的作用.
- 在体内研究涉及条件基因删除 (Il10) 和对IL-10信号的抗体阻断.
主要成果:
- 在CD4+Foxp3-常规T (Tconv) 细胞中,Treg细胞的枯竭诱导了抑制功能.
- 瘤透的Foxp3-Tconv细胞采用了类似Treg的转录特征,并抑制了T细胞活性.
- CD4+ Tconv细胞表达C-C模式受体8 (CCR8) 被确定为瘤中的关键抑制群体.
- 在Treg细胞枯竭后,CCR8+ Tconv细胞在系统和内扩张,调解依赖IL-10的免疫抑制.
- 条件删除T细胞中的IL-10或IL-10信号阻断与Treg细胞枯竭协同,以增强抗瘤免疫力.
结论:
- 传统的T细胞可以在Treg细胞枯竭时获得免疫抑制功能,这代表了治疗耐药性的新机制.
- CCR8+ Tconv细胞是这种二次免疫抑制的关键调解者.
- 针对IL-10信号与Treg细胞枯竭一起提供了一种有希望的策略,以克服癌症免疫治疗中的治疗抵抗.
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