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The M1\/M2 features of MPE-M\u03c6 and their significance to patient outcomes need to be clarified; furthermore, whether M1-repolarization could benefit treatment remains unclear.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Total 147 stage-IV lung adenocarcinoma patients undergoing MPE drainage were enrolled for profiling and validation of their M1\/M2 spectrum. In addition, the MPE-M\u03c6 signature on overall patient survival was analyzed. The impact of the M1-polarization strategy of patient-derived MPE-M\u03c6 on anti-cancer activity was examined.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We found that MPE-M\u03c6 expressed both traditional M1 (HLA-DRA) and M2 (CD163) markers and showed a wide range of M1\/M2 spectrum. Most of the MPE-M\u03c6 displayed diverse PD-L1 expression patterns, while the low PD-L1 expression group was correlated with higher levels of IL-10. Among these markers, we identified a novel two-gene MPE-M\u03c6 signature, IL-1\u03b2 and TGF-\u03b21, representing the M1\/M2 tendency, which showed a strong predictive power in patient outcomes in our MPE-M\u03c6 patient cohort (<jats:italic>N<\/jats:italic>\u2009=\u200960, <jats:italic>p<\/jats:italic>\u2009=\u20090.013) and The Cancer Genome Atlas Lung Adenocarcinoma dataset (<jats:italic>N<\/jats:italic>\u2009=\u2009478, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001). Significantly, \u03b2-glucan worked synergistically with IFN-\u03b3 to reverse the risk signature by repolarizing the MPE-M\u03c6 toward the M1 pattern, enhancing anti-cancer activity.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>We identified MPE-M\u03c6 on the M1\/M2 spectrum and plasticity and described a two-gene M1\/M2 signature that could predict the outcome of late-stage lung cancer patients. In addition, we found that \u201cre-education\u201d of these MPE-M\u03c6 toward anti-cancer M1 macrophages using clinically applicable strategies may overcome tumor immune escape and benefit anti-cancer therapies.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00262-020-02781-8","type":"journal-article","created":{"date-parts":[[2020,11,11]],"date-time":"2020-11-11T15:02:41Z","timestamp":1605106961000},"page":"1435-1450","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["The M1\/M2 spectrum and plasticity of malignant pleural effusion-macrophage in advanced lung cancer"],"prefix":"10.1007","volume":"70","author":[{"given":"Ming-Fang","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-An","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tzu-Hang","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiang-Yuan","family":"Yeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng-Fang","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chin-Lin","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gee-Chen","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ker-Chau","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao-Chi","family":"Ho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5051-9896","authenticated-orcid":false,"given":"Huei-Wen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,11,11]]},"reference":[{"key":"2781_CR1","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.ccm.2017.11.004","volume":"39","author":"R Asciak","year":"2018","unstructured":"Asciak R, Rahman NM (2018) Malignant pleural effusion: from diagnostics to therapeutics. 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The remaining authors declare no conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All experiments were based on the institutional review board (IRB) protocol of the NTUH Research Ethics Committee (IRB approval number: 200709004R and 201604086RINA).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical standards"}},{"value":"MPEs were collected from 147 lung cancer patients with stage IV adenocarcinoma at National Taiwan University Hospital (NTUH) from 2008 to 2020. Written informed consent was collected from all subjects.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}