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

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Title: The upregulation of immune checkpoints after photodynamic therapy reducing immune effect for treating breast cancer.
Authors: Long, Shan1,2,3 (AUTHOR), Wang, Bo1 (AUTHOR), Cui, Yingshu4 (AUTHOR), Shao, Jiakang3,4 (AUTHOR), Zhao, Yibing5 (AUTHOR), Xu, Yuanyuan3 (AUTHOR), Li, Hui3,4 (AUTHOR), Qiu, Haixia3 (AUTHOR), Zhao, Hongyou6 (AUTHOR), Zeng, Jing3 (AUTHOR), Chen, Defu6 (AUTHOR), Li, Xiaosong1,5 (AUTHOR) lixiaosong@hotmail.com, Gu, Ying2,3 (AUTHOR) guyinglaser301@163.com
Source: Lasers in Medical Science. 10/26/2023, Vol. 38 Issue 1, p1-11. 11p.
Subjects: Immune checkpoint proteins, Photodynamic therapy, Breast cancer, T cells, Breast tumors
Abstract: 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. [ABSTRACT FROM AUTHOR]
Copyright of Lasers in Medical Science is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: The upregulation of immune checkpoints after photodynamic therapy reducing immune effect for treating breast cancer.
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  Data: <searchLink fieldCode="AR" term="%22Long%2C+Shan%22">Long, Shan</searchLink><relatesTo>1,2,3</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Wang%2C+Bo%22">Wang, Bo</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Cui%2C+Yingshu%22">Cui, Yingshu</searchLink><relatesTo>4</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Shao%2C+Jiakang%22">Shao, Jiakang</searchLink><relatesTo>3,4</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Zhao%2C+Yibing%22">Zhao, Yibing</searchLink><relatesTo>5</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Xu%2C+Yuanyuan%22">Xu, Yuanyuan</searchLink><relatesTo>3</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Li%2C+Hui%22">Li, Hui</searchLink><relatesTo>3,4</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Qiu%2C+Haixia%22">Qiu, Haixia</searchLink><relatesTo>3</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Zhao%2C+Hongyou%22">Zhao, Hongyou</searchLink><relatesTo>6</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Zeng%2C+Jing%22">Zeng, Jing</searchLink><relatesTo>3</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Chen%2C+Defu%22">Chen, Defu</searchLink><relatesTo>6</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Li%2C+Xiaosong%22">Li, Xiaosong</searchLink><relatesTo>1,5</relatesTo> (AUTHOR)<i> lixiaosong@hotmail.com</i><br /><searchLink fieldCode="AR" term="%22Gu%2C+Ying%22">Gu, Ying</searchLink><relatesTo>2,3</relatesTo> (AUTHOR)<i> guyinglaser301@163.com</i>
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  Data: <searchLink fieldCode="JN" term="%22Lasers+in+Medical+Science%22">Lasers in Medical Science</searchLink>. 10/26/2023, Vol. 38 Issue 1, p1-11. 11p.
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  Data: <searchLink fieldCode="DE" term="%22Immune+checkpoint+proteins%22">Immune checkpoint proteins</searchLink><br /><searchLink fieldCode="DE" term="%22Photodynamic+therapy%22">Photodynamic therapy</searchLink><br /><searchLink fieldCode="DE" term="%22Breast+cancer%22">Breast cancer</searchLink><br /><searchLink fieldCode="DE" term="%22T+cells%22">T cells</searchLink><br /><searchLink fieldCode="DE" term="%22Breast+tumors%22">Breast tumors</searchLink>
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  Label: Abstract
  Group: Ab
  Data: 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. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Lasers in Medical Science is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1007/s10103-023-03894-z
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        Type: general
      – SubjectFull: Photodynamic therapy
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      – SubjectFull: Breast cancer
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      – SubjectFull: T cells
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