Tumor-Associated Macrophage Polarization in Wilms’ Tumor After Neoadjuvant Chemotherapy

TL;DR

This study explores how macrophages in Wilms’ tumor respond to chemotherapy and their potential role as biomarkers or treatment targets.

Contribution

The study characterizes macrophage polarization in Wilms’ tumor after chemotherapy and links it to tumor size and biochemical markers.

Findings

Larger Wilms’ tumors had higher densities of both M1 and M2 macrophages, with M2 macrophages being more prevalent.

The M1/M2 macrophage ratio was higher in regressive subtypes and tumors with elevated creatinine and neuron-specific enolase levels.

Macrophage infiltration was not significantly associated with tumor stage or risk group.

Abstract

While survival rates for Wilms’ tumor are high, a subset of high-risk patients are prone to treatment resistance. Evidence suggests that tumor-associated macrophages may influence therapeutic response. The aim of our study was to characterize macrophage infiltration and polarization in Wilms’ tumors treated with neoadjuvant chemotherapy and to evaluate their association with clinicopathological features. Analysis of tumor samples from 46 patients revealed that larger tumors had a higher density of both M1 and M2 macrophages, with M2 macrophages predominating in general. The M1/M2 ratio was significantly higher in regressive histological subtypes, larger tumors, and in tumors of patients with elevated serum neuron-specific enolase and creatinine. No significant associations were observed between macrophage infiltration and tumor stage or risk group. Macrophage polarization in Wilms’ tumors appears to be associated with tumor burden and selected biochemical parameters, highlighting the potential relevance of macrophages as biomarkers and therapeutic targets.

Background/Objectives: Wilms’ tumor (WT) is the most common malignant renal tumor in childhood, and although survival rates are high, a subset of patients with high-risk disease remain prone to treatment resistance and relapse. Increasing evidence suggests that the tumor microenvironment, particularly tumor-associated macrophages (TAMs), may influence tumor behavior and therapeutic response. This study aimed to characterize M1 and M2 macrophage infiltration in WT treated with neoadjuvant chemotherapy according to the International Society of Pediatric Oncology (SIOP) protocol and to evaluate their association with clinicopathological features. Methods: Tumor tissue samples from 46 pediatric patients were analyzed using double immunohistochemical staining for CD80 (M1) and CD163 (M2) macrophages. TAM density and M1/M2 ratios were quantified in viable tumor areas and correlated with clinical, laboratory, and pathohistological parameters. Results: Total TAM counts were significantly higher in tumors with a volume ≥ 500 mL and in unifocal tumors. Both M1 and M2 macrophages were more abundant in larger tumors; however, M2 macrophages predominated overall. The M1/M2 ratio was positively associated with total TAM counts and was significantly higher in tumors with larger volume, elevated serum neuron-specific enolase, and increased creatinine levels. Regressive histological subtypes exhibited a higher M1/M2 ratio compared with other subtypes. No significant associations were observed between macrophage infiltration and tumor stage or risk group. Conclusions: WT treated with neoadjuvant chemotherapy demonstrates low overall macrophage infiltration with a predominance of M2 macrophages. TAM polarization appears to be associated with tumor burden and selected biochemical parameters, highlighting the potential relevance of macrophages as biomarkers and therapeutic targets in WT.

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