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

• Published in: Gynecologic oncology 2017-10, Vol.147 (1), p.181-187
• Main Authors: Yuan, Xia, Zhang, Jing, Li, Dan, Mao, Ye, Mo, Fei, Du, Wei, Ma, Xuelei
• Format: Article
• Language: English
• Subjects: Antigens, CD - metabolism; Antigens, Differentiation, Myelomonocytic - metabolism; Biomarkers, Tumor - immunology; Cell Count; Female; Humans; Macrophages - immunology; Macrophages - metabolism; Meta-analysis; Ovarian cancer; Ovarian Neoplasms - immunology; Prognosis; Receptors, Cell Surface - metabolism; Survival Analysis; Tumor Microenvironment; Tumor-associated macrophages
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2017.07.007

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. 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. 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. 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. •Higher M1/M2 TAMs ratio in ovarian tumors was associated with a favorable OS and PFS.•High density of CD163+ TAMs might predict poor prognosis in patients with ovarian cancer.•M1 and M2 subsets presented distinct effects on ovarian cancer prognosis.•This suggests that M2 subtypes could be a potential therapeutic target of ovarian cancer.•High density of TAMs was related to advanced TNM stage of ovarian cancer.