The M1/M2 spectrum and plasticity of malignant pleural effusion-macrophage in advanced lung cancer
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ORIGINAL ARTICLE
The M1/M2 spectrum and plasticity of malignant pleural effusion‑macrophage in advanced lung cancer Ming‑Fang Wu1,2 · Chih‑An Lin3 · Tzu‑Hang Yuan1,2,4 · Hsiang‑Yuan Yeh5 · Sheng‑Fang Su6 · Chin‑Lin Guo7 · Gee‑Chen Chang8,9,10,11 · Ker‑Chau Li2,12 · Chao‑Chi Ho3 · Huei‑Wen Chen1,4 Received: 11 December 2019 / Accepted: 22 October 2020 © The Author(s) 2020
Abstract Background Malignant pleural effusion (MPE)-macrophage (Mφ) of lung cancer patients within unique M1/M2 spectrum showed plasticity in M1–M2 transition. The M1/M2 features of MPE-Mφ and their significance to patient outcomes need to be clarified; furthermore, whether M1-repolarization could benefit treatment remains unclear. Methods 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-Mφ signature on overall patient survival was analyzed. The impact of the M1-polarization strategy of patient-derived MPE-Mφ on anti-cancer activity was examined. Results We found that MPE-Mφ expressed both traditional M1 (HLA-DRA) and M2 (CD163) markers and showed a wide range of M1/M2 spectrum. Most of the MPE-Mφ 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-Mφ signature, IL-1β and TGF-β1, representing the M1/M2 tendency, which showed a strong predictive power in patient outcomes in our MPE-Mφ patient cohort (N = 60, p = 0.013) and The Cancer Genome Atlas Lung Adenocarcinoma dataset (N = 478, p
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