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

doi:10.1007/s00262-020-02781-8

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Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/24899

Title:	The M1/M2 spectrum and plasticity of malignant pleural effusion-macrophage in advanced lung cancer
Authors:	Wu, MF;Lin, CA;Yuan, TH;Yeh, HY;Su, SF;Guo, CL;Chang, GC;Li, KC;Ho, CC;Chen, HW
Keywords:	Malignant pleural effusion;Macrophages;Lung cancer
Date:	2021
Issue Date:	2022-08-09T08:09:48Z (UTC)
Publisher:	SPRINGER
ISSN:	0340-7004
Abstract:	Background Malignant pleural effusion (MPE)-macrophage (M phi) of lung cancer patients within unique M1/M2 spectrum showed plasticity in M1-M2 transition. The M1/M2 features of MPE-M phi 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-M phi signature on overall patient survival was analyzed. The impact of the M1-polarization strategy of patient-derived MPE-M phi on anti-cancer activity was examined. Results We found that MPE-M phi expressed both traditional M1 (HLA-DRA) and M2 (CD163) markers and showed a wide range of M1/M2 spectrum. Most of the MPE-M phi 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-M phi signature, IL-1 beta and TGF-beta 1, representing the M1/M2 tendency, which showed a strong predictive power in patient outcomes in our MPE-M phi patient cohort (N = 60, p = 0.013) and The Cancer Genome Atlas Lung Adenocarcinoma dataset (N = 478, p < 0.0001). Significantly, beta-glucan worked synergistically with IFN-gamma to reverse the risk signature by repolarizing the MPE-M phi toward the M1 pattern, enhancing anti-cancer activity. Conclusions We identified MPE-M phi 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-M phi toward anti-cancer M1 macrophages using clinically applicable strategies may overcome tumor immune escape and benefit anti-cancer therapies.
URI:	http://dx.doi.org/10.1007/s00262-020-02781-8 https://www.webofscience.com/wos/woscc/full-record/WOS:000588573900001 https://ir.csmu.edu.tw:8080/handle/310902500/24899
Relation:	CANCER IMMUNOLOGY IMMUNOTHERAPY ,2021 ,v70 ,issue 5 ,p1435-1450
Appears in Collections:	[researcher portal] Artical

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