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
Pages
1435-1450
Date Issued
2021
Author(s)
Wu M.-F.
Lin C.-A.
Yuan T.-H.
Yeh H.-Y.
Guo C.-L.
Chang G.-C.
Li K.-C.
Abstract
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. ? 2020, The Author(s).
SDGs
Other Subjects
antineoplastic agent; B7 antigen; beta glucan; C-C motif chemokine 18; CD163 antigen; gamma interferon; gamma interferon inducible protein 10; HLA DR antigen; interleukin 10; interleukin 1beta; programmed death 1 ligand 1; transforming growth factor beta1; interleukin 1beta; transcriptome; transforming growth factor beta1; tumor marker; adult; advanced cancer; Article; cancer chemotherapy; cancer patient; cancer staging; cancer survival; cancer therapy; chemotherapy; cohort analysis; controlled study; female; flow cytometry; gene expression; genetic marker; human; human cell; in vitro study; lung adenocarcinoma; lung cancer; M1 macrophage; M2 macrophage; major clinical study; male; malignant pleura effusion; overall survival; polarization; priority journal; protein expression; protein fingerprinting; treatment outcome; tumor escape; tumor immunity; validation process; cell culture; cell differentiation; cell plasticity; gene expression regulation; genetics; immunology; lung tumor; macrophage; malignant pleura effusion; metabolism; physiology; Th1 cell; Th2 cell; Biomarkers, Tumor; Cell Differentiation; Cell Plasticity; Cells, Cultured; Gene Expression Regulation, Neoplastic; Humans; Interleukin-1beta; Lung Neoplasms; Macrophages; Neoplasm Staging; Pleural Effusion, Malignant; Th1 Cells; Th2 Cells; Transcriptome; Transforming Growth Factor beta1
Publisher
Springer Science and Business Media Deutschland GmbH
Type
journal article