在抗PD-1检查点封锁后,CMV血清状态与改善的生存率和延迟的毒性开始有关
Gusztav Milotay1,2, Martin Little1,2,3,4, Robert A Watson1,2,3,4
1MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Nature medicine
|April 24, 2025
概括
细胞巨乳病毒 (CMV) 感染对接受免疫检查点阻塞 (ICB) 的黑色素瘤患者的T细胞免疫力产生影响. 冠状病毒阳性与单剂抗PD-1 ICB的更好的生存率和更少的不良事件有关,这表明它具有保护作用.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 病毒学 病毒学
背景情况:
- 细胞巨乳病毒 (CMV) 是一种常见的疹病毒,影响T细胞免疫力.
- 免疫检查点阻塞 (ICB) 是转移性黑色素瘤 (MM) 的关键治疗方法.
- 在黑色素瘤中,CMV感染,T细胞反应和ICB疗效之间的相互作用尚未完全理解.
研究的目的:
- 在接受ICB治疗的转移性黑色素瘤患者中调查CMV感染的瘤后果.
- 探索CMV血清状态对T细胞基因表达和对不同ICB策略的反应的影响.
- 为了确定CMV感染是否影响ICB治疗期间免疫相关不良事件 (irAEs) 的发生率.
主要方法:
- 对接受ICB (抗CTLA-4/抗PD-1或单独抗PD-1) 的转移性黑色素瘤潜在招募患者 (n=341) 的分析.
- 评估T细胞数量,中性粒细胞与淋巴细胞的比率和CD8+T细胞基因表达 (包括TBX21).
- 基于CMV血清状况和ICB治疗方案的整体存活率,复发率和irAEs (结肠炎,肺炎) 发病率的比较.
- 对黑色素瘤患者中CMV血清阳性率的分析与对照和与BRAF突变状态的相关性.
主要成果:
- 通过单剂抗PD-1 ICB,CMV+患者表现出明显的免疫特征,并改善了整体存活率.
- 组合抗CTLA-4/抗PD-1 ICB诱导了CMV患者的CD8+ T细胞中的CMV相关基因表达.
- 确定TBX21表达是CMV相关的CD8+T细胞基因表达的驱动因素,并预测了更好的生存率.
- 在ICB疗法中,CMV+患者的3级+irrAEs发病率显著降低,包括大肠炎和肺炎.
- 在MM患者中,CMV血清阳性较少发生,特别是那些患有BRAF突变黑色素瘤的人,这表明对MM的发展有保护作用.
结论:
- 在接受ICB治疗的黑色素瘤患者中,CMV感染会影响T细胞反应和结果.
- 单剂抗PD-1 ICB疗效在CMV+黑色素瘤患者中得到增强.
- 在ICB期间,CMV感染与严重免疫相关不良事件的风险降低有关.
- 冠状病毒血清状况和BRAF突变状态是黑色素瘤发展和对免疫治疗的反应的重要因素.
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