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Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Malignant 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A 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<jats:italic>via<\/jats:italic>flow cytometry, RNA-sequencing, quantitative PCR, western blot, immunohistochemistry, and other experimental methods.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Intrathoracic 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-\u03b3+, and granzyme B+ CD8+ T cells in the pleural cavity was increased, and the expression of TNF-\u03b1 and IL-1\u03b2 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\u2019 local cytotoxic T cells (CTLs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Intrapleural 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.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2021.760683","type":"journal-article","created":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T16:45:49Z","timestamp":1639413949000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":23,"title":["Intrapleural Injection of Anti-PD1 Antibody: A Novel Management of Malignant Pleural Effusion"],"prefix":"10.3389","volume":"12","author":[{"given":"Xinying","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guannan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suhua","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xincui","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Yin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tangfeng","family":"Lv","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,12,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccm.2017.11.004","article-title":"Malignant Pleural Effusion: From Diagnostics to Therapeutics","volume":"39","author":"Asciak","year":"2018","journal-title":"Clinics Chest Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccm.2020.02.009","article-title":"Management of Malignant Pleural Effusions","volume":"41","author":"Shafiq","year":"2020","journal-title":"Clinics Chest Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0019-2016","article-title":"Malignant Pleural Effusion: From Bench to Bedside","volume":"25","author":"Psallidas","year":"2016","journal-title":"Eur Respir Rev an Off J Eur Respir Soc"},{"key":"B4","doi-asserted-by":"publisher","first-page":"490","DOI":"10.3390\/medicina55080490","article-title":"Malignant Pleural Effusion and Its Current Management: A Review","volume":"55","author":"Skok","year":"2019","journal-title":"Medicina (Kaunas Lithuania)"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3978\/j.issn.2072-1439.2013.09.04","article-title":"Malignant Pleural Effusion and Algorithm Management","volume":"5","author":"Zarogoulidis","year":"2013","journal-title":"J Thorac Dis"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1093\/ejcts\/ezy258","article-title":"ERS\/EACTS Statement on the Management of Malignant Pleural Effusions","volume":"55","author":"Bibby","year":"2019","journal-title":"Eur J cardio-thoracic Surg Off J Eur Assoc Cardio-thoracic Surg"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201807-1415ST","article-title":"Management of Malignant Pleural Effusions. 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