Xia Yuan1, Jing Zhang2, Dan Li3, Ye Mao4, Fei Mo4, Wei Du4, Xuelei Ma5. 1. State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School Sichuan University, Chengdu, PR China. Electronic address: 18382288349@163.com. 2. West China Medical School Sichuan University, Chengdu, PR China. 3. Department of Respiratory Medicine, West China Hospital, West China Medical School Sichuan University, Chengdu, PR China. 4. State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School Sichuan University, Chengdu, PR China. 5. State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School Sichuan University, Chengdu, PR China. Electronic address: drmaxuelei@gmail.com.
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.
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.
Authors: Meghan Travers; Stephen M Brown; Matthew Dunworth; Cassandra E Holbert; Karla R Wiehagen; Kurtis E Bachman; Jackson R Foley; Meredith L Stone; Stephen B Baylin; Robert A Casero; Cynthia A Zahnow Journal: Cancer Res Date: 2019-05-14 Impact factor: 12.701
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