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The M1/M2 spectrum and plasticity of malignant pleural effusion-macrophage in advanced lung cancer
Journal
Cancer Immunology, Immunotherapy
Journal Volume
70
Journal Issue
5
Start Page
1435-1450
ISSN
0340-7004
1432-0851
Date Issued
2020-11-11
Author(s)
Chih-An Lin
Tzu-Hang Yuan
Hsiang-Yuan Yeh
Sheng-Fang Su
Chin-Lin Guo
Ker-Chau Li
Chao-Chi Ho
Huei-Wen Chen
Abstract
<jats:title>Abstract</jats:title><jats:sec>
<jats:title>Background</jats:title>
<jats:p>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.</jats:p>
</jats:sec><jats:sec>
<jats:title>Methods</jats:title>
<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-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.</jats:p>
</jats:sec><jats:sec>
<jats:title>Results</jats:title>
<jats:p>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 (<jats:italic>N</jats:italic> = 60, <jats:italic>p</jats:italic> = 0.013) and The Cancer Genome Atlas Lung Adenocarcinoma dataset (<jats:italic>N</jats:italic> = 478, <jats:italic>p</jats:italic> < 0.0001). Significantly, β-glucan worked synergistically with IFN-γ to reverse the risk signature by repolarizing the MPE-Mφ toward the M1 pattern, enhancing anti-cancer activity.</jats:p>
</jats:sec><jats:sec>
<jats:title>Conclusions</jats:title>
<jats:p>We identified MPE-Mφ 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 “re-education” of these MPE-Mφ toward anti-cancer M1 macrophages using clinically applicable strategies may overcome tumor immune escape and benefit anti-cancer therapies.</jats:p>
</jats:sec>
<jats:title>Background</jats:title>
<jats:p>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.</jats:p>
</jats:sec><jats:sec>
<jats:title>Methods</jats:title>
<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-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.</jats:p>
</jats:sec><jats:sec>
<jats:title>Results</jats:title>
<jats:p>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 (<jats:italic>N</jats:italic> = 60, <jats:italic>p</jats:italic> = 0.013) and The Cancer Genome Atlas Lung Adenocarcinoma dataset (<jats:italic>N</jats:italic> = 478, <jats:italic>p</jats:italic> < 0.0001). Significantly, β-glucan worked synergistically with IFN-γ to reverse the risk signature by repolarizing the MPE-Mφ toward the M1 pattern, enhancing anti-cancer activity.</jats:p>
</jats:sec><jats:sec>
<jats:title>Conclusions</jats:title>
<jats:p>We identified MPE-Mφ 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 “re-education” of these MPE-Mφ toward anti-cancer M1 macrophages using clinically applicable strategies may overcome tumor immune escape and benefit anti-cancer therapies.</jats:p>
</jats:sec>
SDGs
Publisher
Springer Science and Business Media LLC
Type
journal-article