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.