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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:70 |
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| Enthalten in: |
Cancer immunology, immunotherapy : CII - 70(2021), 5 vom: 02. Mai, Seite 1435-1450 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wu, Ming-Fang [VerfasserIn] |
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| Links: |
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| Themen: |
Biomarkers, Tumor |
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| Anmerkungen: |
Date Completed 04.05.2021 Date Revised 30.07.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s00262-020-02781-8 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM317428098 |
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| 100 | 1 | |a Wu, Ming-Fang |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The M1/M2 spectrum and plasticity of malignant pleural effusion-macrophage in advanced lung cancer |
| 264 | 1 | |c 2021 | |
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| 500 | |a Date Revised 30.07.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Lung cancer | |
| 650 | 4 | |a Macrophages | |
| 650 | 4 | |a Malignant pleural effusion | |
| 650 | 7 | |a Biomarkers, Tumor |2 NLM | |
| 650 | 7 | |a Interleukin-1beta |2 NLM | |
| 650 | 7 | |a Transforming Growth Factor beta1 |2 NLM | |
| 700 | 1 | |a Lin, Chih-An |e verfasserin |4 aut | |
| 700 | 1 | |a Yuan, Tzu-Hang |e verfasserin |4 aut | |
| 700 | 1 | |a Yeh, Hsiang-Yuan |e verfasserin |4 aut | |
| 700 | 1 | |a Su, Sheng-Fang |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Chin-Lin |e verfasserin |4 aut | |
| 700 | 1 | |a Chang, Gee-Chen |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Ker-Chau |e verfasserin |4 aut | |
| 700 | 1 | |a Ho, Chao-Chi |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Huei-Wen |e verfasserin |4 aut | |
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