Journal of Innovative Optical Health Sciences, Volume. 17, Issue 1, 2350020(2024)

Anti-PD1 antibody and not anti-LAG-3 antibody improves the antitumor effect of photodynamic therapy for treating metastatic breast cancer

Shan Long1,2, Yibing Zhao3, Yuanyuan Xu2, Bo Wang4, Haixia Qiu2, Hongyou Zhao5, Jing Zeng2, Defu Chen5, Hui Li2,6, Jiakang Shao2,6, Xiaosong Li3、*, and Ying Gu1,2、**
Author Affiliations
  • 1School of Medicine, Nankai University, Tianjin, 300072, P. R. China
  • 2Department of Laser Medicine. The First Medical Center of Chinese PLA General Hospital, Beijing 100853, P. R. China
  • 3Department of Oncology, The Seventh Medical Center of Chinese PLA General Hospital, Beijing 100039, P. R. China
  • 4School of Basic Medicine, Guizhou Medical University, Guiyang 550025, Guizhou, P. R. China
  • 5College of Medical Technology, Beijing Institute of Technology, Beijing 100081, P. R. China
  • 6Medical School of Chinese PLA, Beijing 100853, P. R. China
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    Photodynamic therapy (PDT) has limited effects in treating metastatic breast cancer. Immune checkpoints can deplete the function of immune cells; however, the expression of immune checkpoints after PDT is unclear. This study investigates whether the limited efficacy of PDT is due to upregulated immune checkpoints and tries to combine the PDT and immune checkpoint inhibitor to observe the efficacy. A metastatic breast cancer model was treated by PDT mediated by hematoporphyrin derivatives (HpD-PDT). The anti-tumor effect of HpD-PDT was observed, as well as CD4+T, CD8+T and calreticulin (CRT) by immunohistochemistry and immunofluorescence. Immune checkpoints on T cells were analyzed by flow cytometry after HpD-PDT. When combining PDT with immune checkpoint inhibitors, the antitumor effect and immune effect were assessed. For HpD-PDT at 100mW/cm2 and 40, 60 and 80J/cm2, primary tumors were suppressed and CD4+T, CD8+T and CRT were elevated; however, distant tumors couldn’t be inhibited and survival could not be prolonged. Immune checkpoints on T cells, especially PD1 and LAG-3 after HpD-PDT, were upregulated, which may explain the reason for the limited HpD-PDT effect. After PDT combined with anti-PD1 antibody, but not with anti-LAG-3 antibody, both the primary and distant tumors were significantly inhibited and the survival time was prolonged, additionally, CD4+T, CD8+T, IFN-γ+CD4+T and TNF-α+CD4+T cells were significantly increased compared with HpD-PDT. HpD-PDT could not combat metastatic breast cancer. PD1 and LAG-3 were upregulated after HpD-PDT. Anti-PD1 antibody, but not anti-LAG-3 antibody, could augment the antitumor effect of HpD-PDT for treating metastatic breast cancer.

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    Shan Long, Yibing Zhao, Yuanyuan Xu, Bo Wang, Haixia Qiu, Hongyou Zhao, Jing Zeng, Defu Chen, Hui Li, Jiakang Shao, Xiaosong Li, Ying Gu. Anti-PD1 antibody and not anti-LAG-3 antibody improves the antitumor effect of photodynamic therapy for treating metastatic breast cancer[J]. Journal of Innovative Optical Health Sciences, 2024, 17(1): 2350020

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    Paper Information

    Category: Research Articles

    Received: Feb. 2, 2023

    Accepted: May. 14, 2023

    Published Online: Feb. 28, 2024

    The Author Email: Li Xiaosong (lixiaosong@hotmail.com), Gu Ying (guyinglaser301@163.com)

    DOI:10.1142/S1793545823500207

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