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

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 immu...

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Main Authors: Shan Long, Yibing Zhao, Yuanyuan Xu, Bo Wang, Haixia Qiu, Hongyou Zhao, Jing Zeng, Defu Chen, Hui Li, Jiakang Shao, Xiaosong Li, Ying Gu
Format: Article
Language:English
Published: World Scientific Publishing 2024-01-01
Series:Journal of Innovative Optical Health Sciences
Subjects:
Online Access:https://www.worldscientific.com/doi/10.1142/S1793545823500207
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author Shan Long
Yibing Zhao
Yuanyuan Xu
Bo Wang
Haixia Qiu
Hongyou Zhao
Jing Zeng
Defu Chen
Hui Li
Jiakang Shao
Xiaosong Li
Ying Gu
author_facet Shan Long
Yibing Zhao
Yuanyuan Xu
Bo Wang
Haixia Qiu
Hongyou Zhao
Jing Zeng
Defu Chen
Hui Li
Jiakang Shao
Xiaosong Li
Ying Gu
author_sort Shan Long
collection DOAJ
description 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[Formula: see text]T, CD8[Formula: see text]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 100[Formula: see text]mW/cm2 and 40, 60 and 80[Formula: see text]J/cm2, primary tumors were suppressed and CD4[Formula: see text]T, CD8[Formula: see text]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[Formula: see text]T, CD8[Formula: see text]T, IFN-[Formula: see text]CD4[Formula: see text]T and TNF-[Formula: see text]CD4[Formula: see text]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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spelling doaj.art-cce6705ae830444f8ba279518aed7c132024-01-31T11:09:17ZengWorld Scientific PublishingJournal of Innovative Optical Health Sciences1793-54581793-72052024-01-01170110.1142/S1793545823500207Anti-PD1 antibody and not anti-LAG-3 antibody improves the antitumor effect of photodynamic therapy for treating metastatic breast cancerShan Long0Yibing Zhao1Yuanyuan Xu2Bo Wang3Haixia Qiu4Hongyou Zhao5Jing Zeng6Defu Chen7Hui Li8Jiakang Shao9Xiaosong Li10Ying Gu11School of Medicine, Nankai University, Tianjin, 300072, P. R. ChinaDepartment of Oncology, The Seventh Medical Center of Chinese PLA General Hospital, Beijing 100039, P. R. ChinaDepartment of Laser Medicine. The First Medical Center of Chinese PLA General Hospital, Beijing 100853, P. R. ChinaSchool of Basic Medicine, Guizhou Medical University, Guiyang 550025, Guizhou, P. R. ChinaDepartment of Laser Medicine. The First Medical Center of Chinese PLA General Hospital, Beijing 100853, P. R. ChinaCollege of Medical Technology, Beijing Institute of Technology, Beijing 100081, P. R. ChinaDepartment of Laser Medicine. The First Medical Center of Chinese PLA General Hospital, Beijing 100853, P. R. ChinaCollege of Medical Technology, Beijing Institute of Technology, Beijing 100081, P. R. ChinaDepartment of Laser Medicine. The First Medical Center of Chinese PLA General Hospital, Beijing 100853, P. R. ChinaDepartment of Laser Medicine. The First Medical Center of Chinese PLA General Hospital, Beijing 100853, P. R. ChinaDepartment of Oncology, The Seventh Medical Center of Chinese PLA General Hospital, Beijing 100039, P. R. ChinaSchool of Medicine, Nankai University, Tianjin, 300072, P. R. ChinaPhotodynamic 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[Formula: see text]T, CD8[Formula: see text]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 100[Formula: see text]mW/cm2 and 40, 60 and 80[Formula: see text]J/cm2, primary tumors were suppressed and CD4[Formula: see text]T, CD8[Formula: see text]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[Formula: see text]T, CD8[Formula: see text]T, IFN-[Formula: see text]CD4[Formula: see text]T and TNF-[Formula: see text]CD4[Formula: see text]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.https://www.worldscientific.com/doi/10.1142/S1793545823500207Photodynamic therapyanti-PD1 antibodyanti-LAG-3 antibodyanti-tumor immune effectsmetastatic breast cancer
spellingShingle 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
Journal of Innovative Optical Health Sciences
Photodynamic therapy
anti-PD1 antibody
anti-LAG-3 antibody
anti-tumor immune effects
metastatic breast cancer
title Anti-PD1 antibody and not anti-LAG-3 antibody improves the antitumor effect of photodynamic therapy for treating metastatic breast cancer
title_full Anti-PD1 antibody and not anti-LAG-3 antibody improves the antitumor effect of photodynamic therapy for treating metastatic breast cancer
title_fullStr Anti-PD1 antibody and not anti-LAG-3 antibody improves the antitumor effect of photodynamic therapy for treating metastatic breast cancer
title_full_unstemmed Anti-PD1 antibody and not anti-LAG-3 antibody improves the antitumor effect of photodynamic therapy for treating metastatic breast cancer
title_short Anti-PD1 antibody and not anti-LAG-3 antibody improves the antitumor effect of photodynamic therapy for treating metastatic breast cancer
title_sort anti pd1 antibody and not anti lag 3 antibody improves the antitumor effect of photodynamic therapy for treating metastatic breast cancer
topic Photodynamic therapy
anti-PD1 antibody
anti-LAG-3 antibody
anti-tumor immune effects
metastatic breast cancer
url https://www.worldscientific.com/doi/10.1142/S1793545823500207
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