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

Oncotarget. 2015 Apr 30;6(12):10592-603. 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.

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / blood*
  • Antigens, CD / immunology
  • Antigens, Differentiation, Myelomonocytic / blood*
  • Antigens, Differentiation, Myelomonocytic / immunology
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / immunology
  • Disease-Free Survival
  • Humans
  • Lung Neoplasms / blood*
  • Lung Neoplasms / immunology
  • Lung Neoplasms / therapy*
  • Macrophages / immunology
  • Macrophages / metabolism*
  • Pleural Effusion, Malignant / blood*
  • Pleural Effusion, Malignant / immunology
  • Pleural Effusion, Malignant / therapy*
  • Prognosis
  • Receptors, Cell Surface / blood*
  • Receptors, Cell Surface / immunology

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Biomarkers, Tumor
  • CD163 antigen
  • Receptors, Cell Surface