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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer Berlin Heidelberg
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053174/ https://www.ncbi.nlm.nih.gov/pubmed/33175182 http://dx.doi.org/10.1007/s00262-020-02781-8 |
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author | 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 |
author_facet | 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 |
author_sort | Wu, Ming-Fang |
collection | PubMed |
description | 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00262-020-02781-8) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-8053174 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-80531742021-04-29 The M1/M2 spectrum and plasticity of malignant pleural effusion-macrophage in advanced lung cancer 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 Cancer Immunol Immunother Original Article 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00262-020-02781-8) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2020-11-11 2021 /pmc/articles/PMC8053174/ /pubmed/33175182 http://dx.doi.org/10.1007/s00262-020-02781-8 Text en © The Author(s) 2020 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Article 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 The M1/M2 spectrum and plasticity of malignant pleural effusion-macrophage in advanced lung cancer |
title | The M1/M2 spectrum and plasticity of malignant pleural effusion-macrophage in advanced lung cancer |
title_full | The M1/M2 spectrum and plasticity of malignant pleural effusion-macrophage in advanced lung cancer |
title_fullStr | The M1/M2 spectrum and plasticity of malignant pleural effusion-macrophage in advanced lung cancer |
title_full_unstemmed | The M1/M2 spectrum and plasticity of malignant pleural effusion-macrophage in advanced lung cancer |
title_short | The M1/M2 spectrum and plasticity of malignant pleural effusion-macrophage in advanced lung cancer |
title_sort | m1/m2 spectrum and plasticity of malignant pleural effusion-macrophage in advanced lung cancer |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053174/ https://www.ncbi.nlm.nih.gov/pubmed/33175182 http://dx.doi.org/10.1007/s00262-020-02781-8 |
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