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CD163+ tumor-associated macrophage is a prognostic biomarker and is associated with therapeutic effect on malignant pleural effusion of lung cancer patients

Li Yang, Fei Wang, Liping Wang, Lan Huang, Jing Wang, Bin Zhang and Yi Zhang _

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Oncotarget. 2015; 6:10592-10603. https://doi.org/10.18632/oncotarget.3547

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Abstract

Li Yang1,*, Fei Wang1,2,*, Liping Wang3, Lan Huang1, Jing Wang4, Bin Zhang5 and Yi Zhang1,2,3

1 Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China

2 School of Life Sciences, Zhengzhou University, Zhengzhou, Henan Province, China

3 Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China

4 Department of Respiration, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China

5 Robert H. Lurie Comprehensive Cancer Center, Department of Medicine-Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago IL, USA

* These authors contributed equally to this work

Correspondence to:

Yi Zhang, email:

Liping Wang, email:

Keywords: malignant pleural effusion, tumor-associated macrophages, CD163, prognostic biomarker, therapeutic effect

Received: January 19, 2015 Accepted: February 13, 2015 Published: March 12, 2015

Abstract

CD163+ tumor-associated macrophages (TAMs) play an important role in the progression of cancer. However, the significance of CD163+ TAMs in malignant pleural effusion (MPE) is still unclear. The aim of this study is to evaluate the prognostic value of CD163+ TAMs in MPE, and the regulatory effect of an immune adjuvant (pseudomonas aeruginosa - mannose-sensitive hemagglutinin, PA-MSHA, which is used for MPE treatment in clinic) on CD163+ TAMs in MPE. Here, we found that the percentage of CD163+ TAMs in MPE was significantly higher than that in non-malignant pleural effusion (P<0.001). More importantly, CD163+ TAMs in MPE patients were an independent prognostic factor for progression-free survival. M2-related cytokines were highly expressed in MPE-derived CD163+ TAMs than in MPE-derived CD163- macrophages (P<0.05). CD163+ TAMs frequency in MPE patients was obviously reduced after PA-MSHA treatment in clinic (P<0.05). After treatment with PA-MSHA, M2 macrophages were re-educated to M1 macrophages in vitro. TLR4 blocking antibody inhibited M2 macrophages polarization to M1 macrophages induced by PA-MSHA. These findings highlight that accumulation of CD163+ TAMs in MPE caused by lung cancer is closely correlated with poor prognosis. CD163+ TAMs are associated with therapeutic effect in MPE. PA-MSHA re-educates CD163+ TAMs to M1 macrophages through TLR4-mediated pathway in MPE.


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