Prognostic roles of tumor associated macrophages in urothelial carcinomas: a pooled analysis based on comparative studies

Abstract Emerging evidence indicates that tumor-associated macrophages (TAMs) play diverse roles in the development of various malignancies. However, small sample sizes, variable endpoints, and heterogeneous study designs have led to conflicting results.This pooled analysis seeks to thoroughly assess the relationship between tumor associated macrophages and important survival outcomes for urothelial carcinoma (UC) patients.We systematically searched Web of Science, PubMed, and Embase. The relationship between TAMs and clinical outcomes has been investigated using pooled hazard ratios (HRs) with 95% confidence intervals (CIs). In the meantime, the relationship between TAMs and clinicopathological parameters was further evaluated with pooled odds ratios (ORs) and 95% CIs. A total of 22 comparative studies involving 2638 patients were included for pooled analysis in this study. The pooled results indicated that TAMs identified by CD68 (CD68 + ) have no significant correlation with overall survival (OS) (HR = 1.01, 95%CI = 0.98–1.03, p = 0.723), and recurrence-free survival (RFS) (HR = 1.03, 95%CI = 0.93–1.15, p = 0.543) in UC patients. However, Elevated TAMs identified by CD163 (CD163 + ) were conspicuously associated with unfavorable prognosis regarding OS (HR = 2.28, 95%CI = 1.60–3.26, p < 0.001), and RFS (HR = 2.26, 95%CI = 1.38–3.69, p = 0.001). Moreover, Increased M2 TAMs detected by CD163 or CD204 (CD163 + /CD204 + ) were significantly linked with poorer OS (HR = 2.20, 95%CI = 1.62–2.98, p < 0.001), and worse RFS (HR = 1.93, 95%CI = 1.29–2.90, p = 0.001) in UC patients. Additionally, increased CD163 + TAMs infiltration was an independent risk factor for higher incidence of lymphovascular invasion (LVI) (OR = 2.83, 95%CI = 1.49–5.36, p = 0.001), and carcinoma in situ (Cis) (OR = 1.66, 95%CI = 1.32–2.08, p < 0.001). Meanwhile, elevated CD204 + TAMs suggested higher incidence of multiple lesions (OR = 2.52, 95%CI = 1.08–5.86, p = 0.032) in UC patients. Collectively, the prognostic impact of TAMs is varied in UC patients, the CD163 + , or M2 TAMs (CD163 + and CD204 + ) can be considered as indicative predictors for management of individuals suffering from urothelial carcinoma.