精确的细胞因子调节,以克服瘤微环境驱动的抵抗免疫检查点阻塞
Xiaodong Wang1, Junjie Wang1, Qianqian Wang2
1Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, China.
Biochimica et biophysica acta. Reviews on cancer
|January 25, 2026
概括
细胞因子调节可以在固体瘤中克服免疫检查点抑制剂 (ICI) 的耐药性. 在生物标志物的指导下,放大有益的细胞因子,同时阻断抑制的细胞因子,可以将非响应者转化为持久的ICI响应者.
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:
- 免疫检查点抑制剂 (ICI) 诱导持续缓解,但在大多数固体瘤中面临抵抗.
- 瘤微环境 (TME) 造成T细胞功能障碍,受细胞因子的影响.
- 细胞因子塑造免疫架构,髓质细胞活性和抑制性联体体表达 (例如PD-L1).
研究的目的:
- 提出细胞因子调节的框架,以提高ICI的疗效.
- 综合关于细胞因子-ICI相互作用的机械和临床证据.
- 确定克服ICI耐药性在固体瘤中的策略.
主要方法:
- 对ICI治疗中细胞因子作用的机制和临床证据的审查.
- 对成功和失败的细胞因子-ICI组合的分析.
- 讨论下一代基于细胞因子的治疗方法.
主要成果:
- 提出了一个"推拉"框架:放大Th1/CTL信号 (例如IL-2,IL-12,IL-15,干扰子) 和减弱抑制电路 (例如TGF-β,IL-6,IL-8,IL-10,TNF).
- 系统性暴露,网络冗余和反循环限制了一些工程细胞因子激动剂.
- 某些封锁策略显示出提高有效性和降低毒性的潜力.
结论:
- 下一代解决方案,如瘤激活的前细胞因子和瘤内递送,旨在集中活性并扩大治疗窗口.
- 可操作的生物标志物 (转录组学,血细胞因子,骨髓/中性粒细胞指标,TME概况) 对于患者分层和指导治疗至关重要.
- 生物标志物引导的细胞因子调节提供了一个有前途的策略,将免疫排除的瘤转化为ICI响应者.
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