Prognostic impact of CD204-positive macrophages in lung squamous cell carcinoma: possible contribution of Cd204-positive macrophages to the tumor-promoting microenvironment

J Thorac Oncol. 2012 Dec;7(12):1790-1797. doi: 10.1097/JTO.0b013e3182745968.

Abstract

Introduction: Tumor-associated macrophages (TAMs) are recruited into cancer-induced stroma and produce a specific microenvironment for cancer progression. CD204 (+) TAMs are reportedly related to tumor progression and clinical outcome in some tumors. The aim of this study was to clarify the correlation between CD204 (+) TAMs and the clinicopathological features of lung squamous cell carcinoma.

Methods: We investigated the relationships between the numbers of CD204 (+) TAMs and clinicopathological factors, microvessel density, and the numbers of Foxp3 (+) lymphocytes in 208 consecutively resected cases. We also examined the relationships between the numbers of CD204 (+) TAMs and the expression levels of cytokines involved in the migration and differentiation of CD204 (+) TAMs.

Results: A high number of CD204 (+) TAMs in the stroma was significantly correlated with an advanced p-stage, T factor, N factor, and the presence of vascular and pleural invasion. A high number of CD204 (+) TAMs in the stroma was also a significant prognostic factor for all p-stages and p-stage I. Moreover, the numbers of CD204 (+) TAMs were correlated with the microvessel density and the numbers of Foxp3 (+) lymphocytes. A high number of CD204 (+) TAMs was strongly correlated with the tissue expression level of monocyte chemoattractant protein-1. CD204 (+) TAMs were shown to be significant independent prognostic factors in a multivariate analysis.

Conclusions: CD204 (+) TAMs were an independent prognostic factor in lung squamous cell carcinoma. CD204 (+) TAMs, along with other tumor-promoting stromal cells such as regulatory T cells and endothelial cells, may create tumor-promoting microenvironments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology*
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism*
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoenzyme Techniques
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology*
  • Lymphatic Metastasis
  • Macrophages / metabolism
  • Macrophages / pathology*
  • Male
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Prognosis
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Retrospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction
  • Scavenger Receptors, Class A / genetics
  • Scavenger Receptors, Class A / metabolism*
  • Survival Rate
  • Tumor Microenvironment*

Substances

  • Biomarkers, Tumor
  • CCL2 protein, human
  • Chemokine CCL2
  • MSR1 protein, human
  • RNA, Messenger
  • Scavenger Receptors, Class A