Volume 14 Issue 4
Jul.  2023
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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, 2023, 14(4): 680-690. 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, 2023, 14(4): 680-690. doi: 10.12290/xhyxzz.2023-0159

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

doi: 10.12290/xhyxzz.2023-0159

National Natural Science Foundation of China 81901805

National Natural Science Foundation of China 21976150

National Natural Science Foundation of China 21906135

National High Level Hospital Clinical Research Funding 2022-PUMCH-B-071

National High Level Hospital Clinical Research Funding 2023-PUMCH-E-007

More Information
  • Corresponding author: GUO Zhide, E-mail: gzd666888@xmu.edu.cn; ZHANG Xianzhong, E-mail: zhangxzh@hotmail.com
  • Received Date: 2023-03-29
  • Accepted Date: 2023-04-17
  • Available Online: 2023-05-18
  • Publish Date: 2023-07-30
  • 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-κB/IRF3 and STAT1/3-IRF1 pathways, up-regulating the expression of PD-L1, and increasing the infiltration of pro-inflammatory cytokines, CD8+ T cells and CD4+ T cells in tumors. The combined therapy could increase the infiltration of memory effector T cells, M1 macrophages and dendritic cells which positively regulate immune response, and downregulate immunosuppressive regulatory T cells, M2 macrophages and myeloid-derived suppressor cells. Partial complete remission and immune memory were achieved in tumor-bearing mice treated with combined therapy. It is worth noting that radiodiagnostic agent 2-[18F]FDG combined with anti-PD-L1 mAb could also reprogram the immune microenvironment and significantly improve therapeutic effect. This review presents 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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