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放射性药物联合免疫检查点抑制剂协同抗肿瘤研究新进展

曾馨莹,  文雪君,  郭志德,  张现忠

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文章导航 > 协和医学杂志  > 2023 > 优先出版
曾馨莹, 文雪君, 郭志德, 张现忠. 放射性药物联合免疫检查点抑制剂协同抗肿瘤研究新进展[J]. 协和医学杂志. doi: 10.12290/xhyxzz.2023-0159
引用本文: 曾馨莹, 文雪君, 郭志德, 张现忠. 放射性药物联合免疫检查点抑制剂协同抗肿瘤研究新进展[J]. 协和医学杂志. doi: 10.12290/xhyxzz.2023-0159
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ZENG Xinying, WEN Xuejun, GUO Zhide, ZHANG Xianzhong. Advances in Synergistic Antitumor Effects of Radiopharmaceuticals Combined with Immune Checkpoint Inhibitors[J]. Medical Journal of Peking Union Medical College Hospital. doi: 10.12290/xhyxzz.2023-0159
Citation: ZENG Xinying, WEN Xuejun, GUO Zhide, ZHANG Xianzhong. Advances in Synergistic Antitumor Effects of Radiopharmaceuticals Combined with Immune Checkpoint Inhibitors[J]. Medical Journal of Peking Union Medical College Hospital. doi: 10.12290/xhyxzz.2023-0159
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放射性药物联合免疫检查点抑制剂协同抗肿瘤研究新进展

doi: 10.12290/xhyxzz.2023-0159

  • 1 厦门大学公共卫生学院分子影像暨转化医学研究中心 分子疫苗学与分子 诊断学国家重点实验室, 厦门 361102;

  • 2 中国医学科学院北京协和医院核医学科, 北京 100730;

  • 3 中国医学科学院临床医学研究所, 北京 100730

基金项目: 

国家自然科学基金（81901805,21976150,21906135）

详细信息
    通讯作者:

    郭志德,E-mail:gzd666888@xmu.edu.cn

    张现忠,E-mail:zhangxzh@hotmail.com

  • 中图分类号: R45;R73

Advances in Synergistic Antitumor Effects of Radiopharmaceuticals Combined with Immune Checkpoint Inhibitors

  • 1 State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China;

  • 2 Department of Nuclear Medicine, Peking Union Medical College Hospital & Chinese Academy of Medical Sciences, Beijing 100730, China;

  • 3 Institute of Clinical Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China

Funds: 

National Natural Science Foundation of China（ 81901805,21976150,21906135）

    摘要
  • 摘要: 靶向放射性核素治疗诱导DNA双链断裂，激活cGAS-STING通路、NF-kB/IRF3通路和STAT1/3-IRF1通路，上调程序性细胞死亡配体1 （programmed death ligand-1，PD-L1）的表达，促炎细胞因子、CD8+T细胞及CD4+T细胞在肿瘤中浸润增加，为免疫检查点抑制剂治疗提供了有利的免疫原性微环境。联合治疗使得正向调节免疫反应的记忆效应T细胞、M1型巨噬细胞及树突状细胞浸润增加，免疫抑制性的调节性T细胞、M2型巨噬细胞及髓源性抑制细胞下调，部分小鼠肿瘤完全缓解并产生免疫记忆。值得注意的是，放射性诊断药物2-[18F]FDG联合PD-L1抗体治疗也可调控免疫微环境，显著提高疗效。本文主要综述目前典型的放射性药物联合免疫检查点抑制剂协同抗肿瘤治疗策略，并强调联合治疗时间窗以及不同的治疗组合可能改善治疗效果，提出诊断放射性药物联合免疫治疗有望成为一种新的肿瘤治疗范式，或将成为未来研究的重要方向。
    Abstract: Targeted radionuclide therapy (TRT) provides an immunogenic microenvironment for immune checkpoint inhibitor (ICI) therapy by inducing DNA double-strand break, activating the cGAS-STING, NF-kB/IRF3 and STAT1/3-IRF1 pathways, up-regulating the expression of PD-L1, and increasing the infiltration of proinflammatory cytokines, CD8+ T cells and CD4+ T cells in tumors. The combined therapy regulated the immune microenvironment, that the infiltration of memory effector T cells, M1 macrophages and dendritic cells which positively regulate immune response increased, and immunosuppressive regulatory T cells, M2 macrophages and myeloid-derived suppressor cells were downregulated. And partial complete remission and immune memory were achieved in tumor-bearing mice treated with combined therapy. It's worth noting that radiodiagnostic agent 2-[18F]FDG combined with antiPD-L1 mAb also reprogramed the immune microenvironment and significantly improve therapeutic effect. This review presents the current typical combination therapy strategies, emphasizes the time window of combination therapy and different combinations of therapy that may improve the therapeutic effect, and proposes that radiodiagnostic agents combined with tumor immunotherapy are expected to become a new paradigm and a direction for further research in the future.
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  • 收稿日期:  2023-03-29
  • 网络出版日期:  2023-05-20

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