The Prognostic Value of CD206 in Solid Malignancies: A Systematic Review and Meta-Analysis

SIMPLE SUMMARY: The role of innate immune cells in the tumor microenvironment (TME), more specifically the presence of the tumor associated macrophages (TAMs), is becoming more important in the prognosis and treatment of patients diagnosed with malignancies. The aim of this systematic review and meta-analysis was to assess the potential prognostic value of CD206-expressing TAMs, a subclass of macrophages, which were previously proposed to negatively impact the patient’s prognosis. We identified 27 manuscripts describing the role of CD206 in patient prognosis for 14 different tumor types. Despite a large heterogeneity in the results, we identified a significantly worse overall and disease-free survival for patients with increased CD206-expressing TAMs in the TME. The use of CD206-expressing TAMs could therefore be used as a prognostic marker in patients diagnosed with solid malignancies. ABSTRACT: An increased presence of CD206-expressing tumor associated macrophages in solid cancers was proposed to be associated with worse outcomes in multiple types of malignancies, but contradictory results are published. We performed a reproducible systematic review and meta-analysis to provide increased evidence to confirm or reject this hypothesis following the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. The Embase, Web of Science, and MEDLINE-databases were systematically searched for eligible manuscripts. A total of 27 papers studying the prognostic impact of CD206 in 14 different tumor types were identified. Meta-analyses showed a significant impact on the overall survival (OS) and disease-free survival (DFS). While no significant differences were revealed in progression-free survival (PFS) and disease-specific survival (DSS), a shift towards negative survival was correlated with increased CD206-expresion. As a result of the different tumor types, large heterogeneity was present between the different tumor types. Subgroup analysis of hepatocellular carcinoma and gastric cancers revealed no heterogeneity, associated with a significant negative impact on OS in both groups. The current systematic review displays the increased presence CD206-expressing macrophages as a significant negative prognostic biomarker for both OS and DFS in patients diagnosed with solid cancers. Because a heterogenous group of tumor types was included in the meta-analysis, the results cannot be generalized. These results can, however, be used to further lead follow-up research to validate the specific prognostic value of CD206 in individual tumor types and therapeutic approaches.