The M1/M2 spectrum and plasticity of malignant pleural effusion-macrophage in advanced lung cancer.
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 < 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.


CONCLUSIONS
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.
['Wu|Ming-Fang|MF|', 'Lin|Chih-An|CA|', 'Yuan|Tzu-Hang|TH|', 'Yeh|Hsiang-Yuan|HY|', 'Su|Sheng-Fang|SF|', 'Guo|Chin-Lin|CL|', 'Chang|Gee-Chen|GC|', 'Li|Ker-Chau|KC|', 'Ho|Chao-Chi|CC|', 'Chen|Huei-Wen|HW|http://orcid.org/0000-0001-5051-9896']
D014408:Biomarkers, Tumor D002454:Cell Differentiation D000066670:Cell Plasticity D002478:Cells, Cultured D015972:Gene Expression Regulation, Neoplastic D006801:Humans D053583:Interleukin-1beta D008175:Lung Neoplasms D008264:Macrophages D009367:Neoplasm Staging D016066:Pleural Effusion, Malignant D018417:Th1 Cells D018418:Th2 Cells D059467:Transcriptome D053773:Transforming Growth Factor beta1
Lung cancer Malignant pleural effusion Macrophages