化疗驱动三级淋巴体结构,与转移性卵巢癌中的ICI-响应性TCF1+CD8+T细胞相关
Tereza Lanickova1,2, Michal Hensler1, Lenka Kasikova1
1Sotio Biotech, Prague, Czech Republic.
概括
新辅助化疗增强了卵巢癌中的免疫细胞透,促进了三级淋巴体结构,并保留了ICI敏感的T细胞. 这种组合疗法在高负担瘤中提供了生存益处.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 癌症研究 癌症研究
背景情况:
- 高度血清性卵巢癌 (HGSOC) 由于免疫抑制微环境,对独立免疫检查点抑制剂 (ICI) 的反应有限.
- 传统的化疗药物可以通过调节瘤免疫微环境来增强ICI的疗效.
研究的目的:
- 调查新辅助化疗 (NACT) 对HGSOC的免疫影响,将配对的原发性和转移性病变与NACT原始样本进行比较.
- 评估NACT作为HGSOC中ICI的组合合作伙伴的潜力.
主要方法:
- 在五个患者队伍中使用了转录组,空间和功能测试.
- 在NACT后对结合的原发性和转移性HGSOC活检进行了分析.
- 用Syngeneic HGSOC模型来评估组合治疗的疗效.
主要成果:
- 在转移性HGSOC中,NACT诱导了内等质网膜应激和calreticulin暴露.
- 这导致了免疫透的增加,包括T卵泡辅助细胞 (TFH),促进了三级淋巴体结构 (TLS) 的形成.
- TLS成熟与ICI敏感CD8+T细胞 (TCF1+PD1+) 与ICI不敏感CD8+T细胞 (TIM-3+PD1+) 的较高密度相关.
- 结合化疗和PD-1 ICI在高瘤突变负担HGSOC模型中显著改善了生存率.
结论:
- 在HGSOC中,NACT促进TLS的形成和成熟,保持一种ICI敏感的T细胞表型.
- 在HGSOC中优化临床试验设计,NACT和ICI的战略安排至关重要.
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