التفاصيل البيبلوغرافية
| العنوان: |
The M1/M2 spectrum and plasticity of malignant pleural effusion-macrophage in advanced lung cancer. |
| المؤلفون: |
Wu, Ming-Fang, Lin, Chih-An, Yuan, Tzu-Hang, Yeh, Hsiang-Yuan, Su, Sheng-Fang, Guo, Chin-Lin, Chang, Gee-Chen, Li, Ker-Chau, Ho, Chao-Chi, Chen, Huei-Wen |
| المصدر: |
Cancer Immunology, Immunotherapy; May2021, Vol. 70 Issue 5, p1435-1450, 16p |
| مصطلحات موضوعية: |
LUNG cancer, CANCER patients, PLEURAL effusions, PROGRAMMED death-ligand 1, LUNGS, MACROPHAGES |
| مستخلص: |
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. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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