Intrapleural Injection of Anti-PD1 Antibody: A Novel Management of Malignant Pleural Effusion
BackgroundMalignant tumors accompanied with malignant pleural effusion (MPE) often indicate poor prognosis. The therapeutic effect and mechanism of intrapleural injection of anti-programmed cell death protein 1 (PD1) on MPE need to be explored.MethodsA preclinical MPE mouse model and a small clinica...
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Frontiers Media S.A.
2021-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.760683/full |
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| author | Xinying Li Xinying Li Xinying Li Guannan Wu Guannan Wu Cen Chen Yuan Zhao Yuan Zhao Suhua Zhu Xincui Song Jie Yin Jie Yin Tangfeng Lv Tangfeng Lv Yong Song Yong Song |
| author_facet | Xinying Li Xinying Li Xinying Li Guannan Wu Guannan Wu Cen Chen Yuan Zhao Yuan Zhao Suhua Zhu Xincui Song Jie Yin Jie Yin Tangfeng Lv Tangfeng Lv Yong Song Yong Song |
| author_sort | Xinying Li |
| collection | DOAJ |
| description | BackgroundMalignant tumors accompanied with malignant pleural effusion (MPE) often indicate poor prognosis. The therapeutic effect and mechanism of intrapleural injection of anti-programmed cell death protein 1 (PD1) on MPE need to be explored.MethodsA preclinical MPE mouse model and a small clinical study were used to evaluate the effect of intrapleural injection of anti-PD1 antibody. The role of immune cells was observed via flow cytometry, RNA-sequencing, quantitative PCR, western blot, immunohistochemistry, and other experimental methods.ResultsIntrathoracic injection of anti-PD1 monoclonal antibody (mAb) has significantly prolonged the survival time of mice (P = 0.0098) and reduced the amount of effusion (P = 0.003) and the number of cancer nodules (P = 0.0043). Local CD8+ T cells participated in intrapleural administration of anti-PD1 mAb. The proportion of CD69+, IFN-γ+, and granzyme B+ CD8+ T cells in the pleural cavity was increased, and the expression of TNF-α and IL-1β in MPE also developed significantly after injection. Local injection promoted activation of the CCL20/CCR6 pathway in the tumor microenvironment and further elevated the expression of several molecules related to lymphocyte activation. Clinically, the control rate of intrathoracic injection of sintilimab (a human anti-PD1 mAb) for 10 weeks in NSCLC patients with MPE was 66.7%. Local injection improved the activity and function of patients’ local cytotoxic T cells (CTLs).ConclusionsIntrapleural injection of anti-PD1 mAb could control malignant pleural effusion and the growth of cancer, which may be achieved by enhancing local CTL activity and cytotoxicity. |
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| language | English |
| last_indexed | 2024-12-24T03:07:22Z |
| publishDate | 2021-12-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-5883676518594af6a1a43daf829184ea2022-12-21T17:17:57ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-12-011210.3389/fimmu.2021.760683760683Intrapleural Injection of Anti-PD1 Antibody: A Novel Management of Malignant Pleural EffusionXinying Li0Xinying Li1Xinying Li2Guannan Wu3Guannan Wu4Cen Chen5Yuan Zhao6Yuan Zhao7Suhua Zhu8Xincui Song9Jie Yin10Jie Yin11Tangfeng Lv12Tangfeng Lv13Yong Song14Yong Song15Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, ChinaDepartment of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, Nanjing University School of Medicine, Nanjing, ChinaNanjing University Institute of Respiratory Medicine, Nanjing, ChinaDepartment of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, ChinaNanjing University Institute of Respiratory Medicine, Nanjing, ChinaDepartment of Respiratory and Critical Care Medicine, Jinling Hospital, Southern Medical University (Guangzhou), Nanjing, ChinaDepartment of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, ChinaNanjing University Institute of Respiratory Medicine, Nanjing, ChinaDepartment of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, ChinaDepartment of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, ChinaDepartment of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, ChinaNanjing University Institute of Respiratory Medicine, Nanjing, ChinaDepartment of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, ChinaNanjing University Institute of Respiratory Medicine, Nanjing, ChinaDepartment of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, ChinaNanjing University Institute of Respiratory Medicine, Nanjing, ChinaBackgroundMalignant tumors accompanied with malignant pleural effusion (MPE) often indicate poor prognosis. The therapeutic effect and mechanism of intrapleural injection of anti-programmed cell death protein 1 (PD1) on MPE need to be explored.MethodsA preclinical MPE mouse model and a small clinical study were used to evaluate the effect of intrapleural injection of anti-PD1 antibody. The role of immune cells was observed via flow cytometry, RNA-sequencing, quantitative PCR, western blot, immunohistochemistry, and other experimental methods.ResultsIntrathoracic injection of anti-PD1 monoclonal antibody (mAb) has significantly prolonged the survival time of mice (P = 0.0098) and reduced the amount of effusion (P = 0.003) and the number of cancer nodules (P = 0.0043). Local CD8+ T cells participated in intrapleural administration of anti-PD1 mAb. The proportion of CD69+, IFN-γ+, and granzyme B+ CD8+ T cells in the pleural cavity was increased, and the expression of TNF-α and IL-1β in MPE also developed significantly after injection. Local injection promoted activation of the CCL20/CCR6 pathway in the tumor microenvironment and further elevated the expression of several molecules related to lymphocyte activation. Clinically, the control rate of intrathoracic injection of sintilimab (a human anti-PD1 mAb) for 10 weeks in NSCLC patients with MPE was 66.7%. Local injection improved the activity and function of patients’ local cytotoxic T cells (CTLs).ConclusionsIntrapleural injection of anti-PD1 mAb could control malignant pleural effusion and the growth of cancer, which may be achieved by enhancing local CTL activity and cytotoxicity.https://www.frontiersin.org/articles/10.3389/fimmu.2021.760683/fullmalignant pleural effusion (MPE)intrapleural injectionanti-PD1cytotoxic T lymphocyte (CTL)tumor microenvironment (TME) |
| spellingShingle | Xinying Li Xinying Li Xinying Li Guannan Wu Guannan Wu Cen Chen Yuan Zhao Yuan Zhao Suhua Zhu Xincui Song Jie Yin Jie Yin Tangfeng Lv Tangfeng Lv Yong Song Yong Song Intrapleural Injection of Anti-PD1 Antibody: A Novel Management of Malignant Pleural Effusion Frontiers in Immunology malignant pleural effusion (MPE) intrapleural injection anti-PD1 cytotoxic T lymphocyte (CTL) tumor microenvironment (TME) |
| title | Intrapleural Injection of Anti-PD1 Antibody: A Novel Management of Malignant Pleural Effusion |
| title_full | Intrapleural Injection of Anti-PD1 Antibody: A Novel Management of Malignant Pleural Effusion |
| title_fullStr | Intrapleural Injection of Anti-PD1 Antibody: A Novel Management of Malignant Pleural Effusion |
| title_full_unstemmed | Intrapleural Injection of Anti-PD1 Antibody: A Novel Management of Malignant Pleural Effusion |
| title_short | Intrapleural Injection of Anti-PD1 Antibody: A Novel Management of Malignant Pleural Effusion |
| title_sort | intrapleural injection of anti pd1 antibody a novel management of malignant pleural effusion |
| topic | malignant pleural effusion (MPE) intrapleural injection anti-PD1 cytotoxic T lymphocyte (CTL) tumor microenvironment (TME) |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.760683/full |
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