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Therefore, the search for therapeutic drugs to transform MPE to functionally \u201chot\u201d one could advance the development of effective immunotherapeutic strategy. Herein, translational selenium nanoparticles coated with immune\u2010modulating macromolecule lentinan (SeNPs@LNT) are designed to restore the dysfunctional immune cells in patient\u2010derived MPE microenvironment. Internalization of the SeNPs@LNT can effectively reduce the immunosuppressive status by enhancing the proliferation of CD4<jats:sup>+<\/jats:sup> T cells and natural killer cells, and remodeling the tumor associated macrophages into tumoricidal M1 phenotype in MPE derived from patients presenting low Se levels in blood and pleural effusion. Th1, cytotoxic T cell, <jats:italic>\u03b3\u03b4<\/jats:italic> T, and B cell functions are upregulated, and Th2, Th17, and Treg cells activity is downregulated. Furthermore, SeNPs@LNT can be gradually metabolized into SeCys2 to promote the production of metabolites associated with tumor growth inhibition and immune response activation in MPE microenvironment. In contrast, lung cancer markers and vitamin B6 metabolism are decreased. The translational SeNP\u2010based nanotherapeutic strategy restores functional \u201ccold\u201d MPE to \u201chot\u201d MPE to activate the immune responses of various immune cells in MPE of lung cancer patients.<\/jats:p>","DOI":"10.1002\/adhm.202100149","type":"journal-article","created":{"date-parts":[[2021,4,19]],"date-time":"2021-04-19T00:46:44Z","timestamp":1618793204000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Translational Nanotherapeutics Reprograms Immune Microenvironment in Malignant Pleural Effusion of Lung Adenocarcinoma"],"prefix":"10.1002","volume":"10","author":[{"given":"Zhenhuan","family":"Song","sequence":"first","affiliation":[{"name":"Research Center of Cancer Diagnosis and Therapy Department of Oncology The First Affiliated Hospital and Department of Chemistry Jinan University  Guangzhou 510632 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weizhan","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Respiratory Disease The State Key Laboratory of Respiratory Disease China Clinical Research Centre for Respiratory Disease Guangzhou Institute of Respiratory Disease First Affiliated Hospital of Guangzhou Medical University  Guangzhou 510120 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haichong","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Respiratory Disease The State Key Laboratory of Respiratory Disease China Clinical Research Centre for Respiratory Disease Guangzhou Institute of Respiratory Disease First Affiliated Hospital of Guangzhou Medical University  Guangzhou 510120 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunxiang","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Respiratory Disease The State Key Laboratory of Respiratory Disease China Clinical Research Centre for Respiratory Disease Guangzhou Institute of Respiratory Disease First Affiliated Hospital of Guangzhou Medical University  Guangzhou 510120 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinlin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Respiratory Disease The State Key Laboratory of Respiratory Disease China Clinical Research Centre for Respiratory Disease Guangzhou Institute of Respiratory Disease First Affiliated Hospital of Guangzhou Medical University  Guangzhou 510120 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6953-1342","authenticated-orcid":false,"given":"Tianfeng","family":"Chen","sequence":"additional","affiliation":[{"name":"Research Center of Cancer Diagnosis and Therapy Department of Oncology The First Affiliated Hospital and Department of Chemistry Jinan University  Guangzhou 510632 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,4,18]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21492"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/ejcts\/ezy258"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/1759-7714.12877"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aat5690"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2018.1554969"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-019-0590-4"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aay9789"},{"key":"e_1_2_8_8_1","first-page":"4587","volume":"37","author":"Chu H. 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