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

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

doi:10.18632/oncotarget.3547

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.

Highlights

Malignant pleural effusion (MPE) is a frequent problem faced by clinicians, which is usually associated with cancer-related mortality and morbidity, and reduces the quality of life as well [1, 2]
The results showed that the percentage of CD163+CD14+ cells was significantly higher in MPE than that in non-malignant pleural effusion (NMPE) (P
These data indicate that the level of CD163+ tumor-associated macrophages (TAMs) is increased in MPE caused by lung cancer

Summary

Introduction

Malignant pleural effusion (MPE) is a frequent problem faced by clinicians, which is usually associated with cancer-related mortality and morbidity, and reduces the quality of life as well [1, 2]. MPE is a complication that occurs in 30% of lung cancers. It can occur with other cancers, such as breast cancers and lymphomas. The main goals in the treatment of MPE are the removal of effusion, the improvement in symptoms and the prevention of re-accumulation. Therapeutic thoracentesis and fluid aspiration should be the first medical procedure in the management of MPE which are useful in determining the effects on breathlessness. Thoracentesis has limited effect as a permanent therapeutic approach. Chemotherapy is effective in controlling the production only in non-small cell of lung cancer (NSCLC) patients [3]

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