Prognostic significance of tumor-associated macrophages in ovarian cancer: A meta-analysis

Gynecol Oncol. 2017 Oct;147(1):181-187. doi: 10.1016/j.ygyno.2017.07.007. Epub 2017 Jul 8.

Abstract

Objective: The role of tumor-associated macrophages (TAMs) in tumor microenvironment remains controversial due to the two different polarized subsets of TAMs. Here, we performed a meta-analysis to evaluate the correlation between subpopulations of TAMs and clinical outcomes in patients with ovarian cancer.

Methods: A comprehensive search in PUBMED/Medline and EMBASE databases was performed. The association between TAMs and patient prognosis of ovarian cancer was estimated with hazard ratios (HRs) and their corresponding 95% confidence intervals (95% CIs) using a random-effect model. Additionally, sensitivity analysis and Begg's test were conducted.

Results: Nine studies including 794 patients were enrolled in the meta-analysis. The results showed that higher M1/M2 ratio in tumor tissues was associated with a favorable overall survival (OS) (HR=0.449, 95% CI=0.283-0.712, P=0.001). Elevated intra-islet M1/M2 TAMs ratio showed a positive correlation for OS (HR=0.510, 95% CI=0.264-0.986, P=0.045). No significant relation was observed between OS and CD68+ TAMs (HR=0.99, 95% CI=0.88-1.11, P=0.859), CD163+ TAMs (HR=1.04, 95% CI=0.92-1.16, P=0.544) or CD163+/CD68+ TAMs ratio (HR=1.628, 95% CI=0.529-5.008, P=0.395). Worse progression-free survival (PFS) was associated with high density of CD163+ TAMs (HR=2.157, 95% CI=1.406-3.312, P=0.000) and higher ratio of CD163+/CD68+ TAMs (HR=3.223, 95% CI=1.805-5.755, P=0.000). Elevated M1/M2 TAMs ratio predicted better PFS of ovarian cancer (HR=0.490, 95% CI=0.270-0.890, P=0.019). Furthermore, high density of CD163+ and CD68+ TAMs was observed in ovarian cancer with advanced TNM stage.

Conclusion: In our study, it was revealed that CD163+ TAMs infiltration was associated with poor prognosis of ovarian cancer and high M1/M2 macrophages ratio in tumor tissues predicted better prognosis.

Keywords: Meta-analysis; Ovarian cancer; Prognosis; Tumor-associated macrophages.

Publication types

  • Meta-Analysis

MeSH terms

  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Biomarkers, Tumor / immunology
  • Cell Count
  • Female
  • Humans
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Ovarian Neoplasms / immunology*
  • Prognosis
  • Receptors, Cell Surface / metabolism
  • Survival Analysis
  • Tumor Microenvironment

Substances

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