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Clinical Research Papers:

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

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

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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.