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

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.