The upregulation of immune checkpoints after photodynamic therapy reducing immune effect for treating breast cancer

Shan Long, Bo Wang, Yingshu Cui, Jiakang Shao, Yibing Zhao, Yuanyuan Xu, Hui Li, Haixia Qiu, Hongyou Zhao, Jing Zeng, Defu Chen, Xiaosong Li*, Ying Gu*

*此作品的通讯作者

科研成果: 期刊稿件文章同行评审

摘要

The immune effect induced by photodynamic therapy (PDT) has a limited effect on breast tumor. This study hypothesized that suppressive immune checkpoints on T cells might upregulate after PDT, which may reduce the antitumor effect of PDT for treating breast tumor. This study explored the alteration of immune checkpoint for the first time. A bilateral subcutaneous transplanted breast tumor mice model was established, and right tumors imitated primary tumors, and left tumors imitated distant tumors. Primary tumors were treated with PDT mediated by hematoporphyrin derivatives (HpD-PDT). Costimulatory molecules (ICOS, OX40, and 4-1BB) and immune checkpoints (PD1, LAG-3, CTLA-4, TIM-3, TIGIT) on tumor infiltrating T cells after HpD-PDT were analyzed by flow cytometry. Antitumor and immune effects were also assessed after HpD-PDT combined with anti-PD1 and LAG-3 antibodies. Primary tumors were suppressed, but distant tumors could not be inhibited after HpD-PDT. The number of T cells was increased, but function did not enhance after HpD-PDT. Additionally, costimulatory molecules (ICOS, OX40, and 4-1BB) were not elevated, but the suppressive immune checkpoints on tumor infiltrating T cells were upregulated after HpD-PDT. Notably, PD1+ LAG-3+ CD4+ T and PD1+ LAG-3+ CD8+ T cells were significantly increased. When PD1 and LAG-3 blockade combined with HpD-PDT, both primary and distant tumors were significantly suppressed, and antitumor immune effects were significantly enhanced. HpD-PDT could upregulate the PD1+ LAG-3+ CD4+ T and PD1+ LAG-3+ CD8+ T cells. Dual blockade of PD1 and LAG-3 immune checkpoints can enhance the antitumor effect of HpD-PDT.

源语言英语
文章编号243
期刊Lasers in Medical Science
38
1
DOI
出版状态已出版 - 12月 2023

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Long, S., Wang, B., Cui, Y., Shao, J., Zhao, Y., Xu, Y., Li, H., Qiu, H., Zhao, H., Zeng, J., Chen, D., Li, X., & Gu, Y. (2023). The upregulation of immune checkpoints after photodynamic therapy reducing immune effect for treating breast cancer. Lasers in Medical Science, 38(1), 文章 243. https://doi.org/10.1007/s10103-023-03894-z