表皮/imcDC2轴促进了人类NSCLC中新辅助抗PD-1的抵抗
Yongyuan Chen1,2, Zheyu Shao1,2, Zhixing Hao1,2
1Department of Thoracic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Journal for immunotherapy of cancer
|August 12, 2024
概括
在非小细胞肺癌 (NSCLC) 中,新辅助剂抗PD-1 治疗耐药性与抑制CD8+ T细胞的加勒-9+癌细胞有关. 与PD-1一起阻断TIM-3可以通过恢复T细胞功能来克服这种抵抗.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 翻译医学是一种翻译医学.
背景情况:
- 对免疫检查点抑制剂 (ICI) 的治疗耐药性限制了长期益处.
- 在非小细胞肺癌 (NSCLC) 中新辅助剂抗PD-1 耐药性背后的机制尚未完全理解.
研究的目的:
- 阐明NSCLC中新辅助抗PD-1疗法的初级耐药性机制.
- 确定预测对新辅助抗PD-1疗法的反应和耐药性的生物标志物.
- 探索克服抗性的治疗策略.
主要方法:
- 对NSCLC患者样本进行多omics分析 (质量细胞计,scRNA-seq,散装RNA-seq,多色流细胞计).
- 在体外实验中对原始细胞和细胞系进行实验.
- 在体内研究使用易斯携带的小鼠模型.
主要成果:
- 增加的CD8+组织内存T细胞 (TRMs) 与疗效相关;增加的CD1c+未成熟的经典2型树突细胞 (imcDC2) 和加列-9+癌细胞与耐药性相关.
- 一个涉及加勒-9/TIM-3的表皮/imcDC2抑制轴抑制CD8+TRM抗瘤反应.
- CD8+TRMs和加列-9+癌细胞的基因表达预测了临床结果.
结论:
- 加列-9表达瘤细胞通过加列-9/TIM-3通过抑制imcDC2和CD8+TRMs驱动NSCLC中新辅助抗PD-1疗法的初级耐药性.
- 将抗TIM-3与抗PD-1疗法结合起来,可以破坏这种抑制循环并克服抵抗.
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