Characterization of the Inflammatory Microenvironment and Identification of Potential Therapeutic Targets in Wilms Tumors

Abstract

The role of inflammation in cancer has been reported in various adult malignant neoplasms. By contrast, its role in pediatric tumors has not been as well studied. In this study, we have identified and characterized the infiltration of various inflammatory immune cells as well as inflammatory markers in Wilms tumor (WT), the most common renal malignancy in children. Formalin-fixed paraffin-embedded blocks from tumors and autologous normal kidneys were immunostained for inflammatory immune cells (T cells, B cells, macrophages, neutrophils, and mast cells) and inflammatory markers such as cyclooxygenase-2 (COX-2), hypoxia-inducible factor 1α, phosphorylated STAT3, phosphorylated extracellular signal–related kinases 1 and 2, inducible nitric oxide synthase, nitrotyrosine, and vascular endothelial growth factor expression. Overall, we found that there was predominant infiltration of tumor-associated macrophages in the tumor stroma where COX-2 was robustly expressed. The other tumor-associated inflammatory markers were also mostly localized to tumor stroma. Hence, we speculate that COX-2–mediated inflammatory microenvironment may be important in WT growth and potential therapies targeting this pathway may be beneficial and should be tested in clinical settings for the treatment of WTs in children.