Clinicopathologic and prognostic significance of tumor-associated macrophages in patients with hepatocellular carcinoma: A meta-analysis

PURPOSE: Tumor-associated macrophages (TAMs) deserve more focus because of its clinicopathologic and prognostic roles in solid tumors. However, the prognostic value of TAMs in patients with hepatocellular carcinoma (HCC) is still controversial. We performed a meta-analysis to resolve the issue. METHODS: We selected relevant studies from the Cochrane Library, Embase and PubMed databases. The hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated employing fixed-effect or random-effect models depending on the heterogeneity of the included trials. Moreover, we also performed subgroup analysis, cumulative meta-analysis, sensitivity analysis, and bias analysis (Egger’s test). RESULTS: A total of 20 observational studies with 4297 patients were enrolled. For TAMs subsets, high density of CD68+ TAMs in either intratumor (IT) (pooled HR = 1.417; 95% CI = 1.092–1.839; P = 0.009) or peritumor (PT) (pooled HR = 1.393; 95% CI = 1.022–1.899; P = 0.036) was associated with a poor OS. High density of CD68+ TAMs in IT was also associated with high AFP value, large tumor size, absent encapsulation, present vascular invasion, and later tumor-nodes-metastasis (TNM) stage. High density of CD163+ macrophages in serum was associated with a poor OS (pooled HR = 5.698; 95% CI = 3.062–10.603; P < 0.001). High density of CD204+ TAMs in IT was associated with a poor OS (pooled HR = 1.947; 95% CI = 1.387–2.733; P < 0.001. High density of CD206+ TAMs in IT was associated with a poor OS (pooled HR = 1.723; 95% CI = 1.308–2.270; P < 0.001) and DFS (pooled HR = 1.711; 95% CI = 1.214–2.412; P = 0.002). However, high density of CD169+ TAMs in IT was associated with a good OS (pooled HR = 0.471; 95% CI = 0.343–0.647; P = 0.037). CONCLUSIONS: TAMs could serve as independent predictive indicators and therapeutic targets for HCC. Further trials are needed to elucidate the exact relationship and the underlying mechanism.