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免疫检查点抑制剂对非小细胞肺癌的时间效应

Xinyue Guo¹, Lanqun Qin^1,2, Xinmeng Wang¹

¹Oncology Department, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou Second People's Hospital, Changzhou, China.

|January 8, 2025

概括

昼夜节律对非小细胞肺癌 (NSCLC) 免疫疗法的疗效产生影响. 免疫检查点抑制剂 (ICI) 的早晨给药在小鼠中显示出更好的结果,但人类试验表明,下午治疗改善了无进展的生存率.

科学领域:

时间生物学和免疫学.
瘤学和癌症治疗学癌症治疗学

背景情况:

昼夜节律或24小时生理周期与免疫功能和瘤发育密切相关.
虽然化疗和放射治疗表现出时间依赖的效果,但治疗时间对免疫疗法的影响仍未得到充分研究.

研究的目的:

研究昼夜节律定时对免疫检查点抑制剂 (ICI) 在非小细胞肺癌 (NSCLC) 的疗效的影响.
探索NSCLC免疫治疗的潜在时间依赖的治疗策略.

主要方法:

构建了C57BL/6N肺部易斯癌症小鼠模型,并在早上7点或晚上7点给予抗PD-1抗体.
在小鼠中使用PCR评估PD-L1表达通过流细胞计和时钟基因 (BMAL1,PER2) 表达.
在2020年6月至2022年12月期间对用ICI治疗的NSCLC患者进行了回顾性分析.

主要成果:

早上接受ICI治疗的小鼠表现出较慢的瘤生长和瘤体积减少,BMAL1/PER2表达增加和PD-L1.1抑制.
追溯分析显示,在下午 (下午12:00后) 接受ICI治疗的患者与早晨 (下午12:00前) 治疗 (9.8个月) 相比,无进展生存期 (16.5个月) 显著更长.

结论:

免疫疗法,特别是NSCLC的ICI,显示出时间依赖的疗效,表明一种新的治疗策略.
优化基于昼夜节律的ICI施用时间可能会改善NSCLC患者的治疗结果.

关键词:

时间效应时间效应.昼夜节律昼夜节律免疫检查点抑制剂免疫检查点抑制剂非小细胞肺癌的肺癌.

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