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免疫检查点抑制剂治疗晚期非小细胞肺癌的预后标志物动态监测研究进展

代丽源 石远凯 韩晓红

代丽源, 石远凯, 韩晓红. 免疫检查点抑制剂治疗晚期非小细胞肺癌的预后标志物动态监测研究进展[J]. 协和医学杂志, 2022, 13(2): 287-295. doi: 10.12290/xhyxzz.2021-0608
引用本文: 代丽源, 石远凯, 韩晓红. 免疫检查点抑制剂治疗晚期非小细胞肺癌的预后标志物动态监测研究进展[J]. 协和医学杂志, 2022, 13(2): 287-295. doi: 10.12290/xhyxzz.2021-0608
DAI Liyuan, SHI Yuankai, HAN Xiaohong. Advances in Dynamic Monitoring of Immune Checkpoint Inhibitors as the Prognostic Markers for Advanced Non-small Cell Lung Cancer[J]. Medical Journal of Peking Union Medical College Hospital, 2022, 13(2): 287-295. doi: 10.12290/xhyxzz.2021-0608
Citation: DAI Liyuan, SHI Yuankai, HAN Xiaohong. Advances in Dynamic Monitoring of Immune Checkpoint Inhibitors as the Prognostic Markers for Advanced Non-small Cell Lung Cancer[J]. Medical Journal of Peking Union Medical College Hospital, 2022, 13(2): 287-295. doi: 10.12290/xhyxzz.2021-0608

免疫检查点抑制剂治疗晚期非小细胞肺癌的预后标志物动态监测研究进展

doi: 10.12290/xhyxzz.2021-0608
基金项目: 

国家“重大新药创制”科技重大专项 2019ZX09201-002

国家“重大新药创制”科技重大专项 2017ZX09304015

2022首都卫生发展科研专项 2022-2z-4016

详细信息
    通讯作者:

    韩晓红,E-mail:hanxiaohong@pumch.cn

  • 中图分类号: R734.2; R730.3

Advances in Dynamic Monitoring of Immune Checkpoint Inhibitors as the Prognostic Markers for Advanced Non-small Cell Lung Cancer

Funds: 

Chinese National Major Project for New Drug Innovation 2019ZX09201-002

Chinese National Major Project for New Drug Innovation 2017ZX09304015

2022 Capital Health Development Scientific Research Project 2022-2z-4016

More Information
  • 摘要: 免疫检查点抑制剂在晚期非小细胞肺癌中的应用显著提高了患者的生存获益,但存在治疗反应率低等临床问题。免疫检查点抑制剂治疗是肿瘤-免疫系统交互对话、动态变化的过程,纵向监测生物标志物变化,有助于消除个体间的差异,提供肿瘤时空异质性信息。本文将从肿瘤细胞源性、免疫微环境源性及多指标联合三方面对免疫检查点抑制剂治疗晚期非小细胞肺癌预后标志物动态监测的相关研究进展进行综述。
    作者贡献:代丽源负责文献检索、论文撰写及修订;韩晓红、石远凯负责论文选题和审校。
    利益冲突:所有作者均声明不存在利益冲突
  • 表  1  ICIs治疗晚期NSCLC预后标志物动态监测相关研究

    标志物 治疗方式 样本量(n) 检测内容 监测方法 临床效应 参考文献
    ctDNA nivolumab 14 基因等位频率AF 靶向测序(53个基因) PD [25]
    抗PD-1单药/联合ICIs治疗 28 突变体等位基因分数MAF 高通量基因测序 PR、PFS、OS [26]
    pembrolizumab 12 bTMB、最大体细胞等位基因频率MSAF、肿瘤克隆结构 靶向测序(329个基因) PFS、肿瘤进展 [27]
    nivolumab/pembrolizumab/atezolizumab 34 KRAS突变 微滴式数字PCR PFS、OS、肿瘤进展 [28]
    CTC nivolumab 24 PD-L1+ CTCs 循环肿瘤细胞检测体系(Cell Search System) PD、CB [29]
    CD4+ T细胞亚群 atezolizumab/nivolumab/pembrolizumab 70 CD28 CD4+ T细胞 流式细胞术 HPD [30]
    CD8+ T细胞亚群 pembrolizumab/nivolumab 36 表达CX3CR1的CD8+T细胞 流式细胞术 ORR、PFS、OS [31]
    TCR nivolumab 4 TCR克隆性 单细胞RNA测序 肿瘤进展 [32]
    nivolumab 21 TCR克隆性 TCR测序 MPR [33]
    nivolumab 40 PD-1+CD8+T细胞 流式细胞术TCR测序 PFS [34]
    NLR nivolumab 101 NLR 全自动血液分析仪 PFS [35]
    nivolumab/pembrolizumab 19 NLR 全自动血液分析仪 TTF [36]
    LMR nivolumab 162 LMR 全自动血液分析仪 ORR、PFS、OS [37]
    IL-8 nivolumab/pembrolizumab 19 IL-8 酶联免疫吸附试验 假性进展 [38]
    IL-6 nivolumab/pembrolizumab/atezolizumab/durvalumab 47 IL-6 酶联免疫吸附试验 PFS [39]
    ctDNA、TCR nivolumab/pembrolizumab/联合ICIs治疗 38 ctDNA、TCR克隆性 靶向错误矫正测序 PFS、OS [40]
    bTMB、CD8+T细胞亚群、ctDNA 抗PD-1单药/联合ICIs治疗 99 ctDNA、CD8+ T细胞 高通量测序流式细胞术 PFS [41]
    NSCLC:非小细胞肺癌;ctDNA:循环肿瘤DNA;PD-1:程序性死亡蛋白-1;ICIs:免疫检查点抑制剂;CTC:循环肿瘤细胞;PD-L1:程序性死亡[蛋白]配体-1;NLR:中性粒细胞/淋巴细胞比值;LMR:淋巴细胞/单核细胞比值;IL-8:白细胞介素-8;TCR:T细胞受体;bTMB:血液肿瘤突变负荷;DCB:持久临床获益;PR:部分缓解;PFS:无进展生存期;OS:总生存期;PD:疾病进展;CB:临床获益;HPD:超进展;ORR:客观缓解率;MPR:病理部分缓解;TTF:达到治疗失败时间
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出版历程
  • 收稿日期:  2021-08-22
  • 录用日期:  2021-10-13
  • 网络出版日期:  2022-03-14
  • 刊出日期:  2022-03-30

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