# Differential immune infiltrates in histomorphologic Wilms tumor regions identify prognostic macrophages

## TL;DR

This study finds that immune cell patterns in different parts of Wilms tumors can predict patient outcomes, especially for intermediate-risk cases.

## Contribution

The study identifies region-specific immune markers (CD206, CD86, CD68) in Wilms tumor histomorphology that correlate with prognosis and relapse timing.

## Key findings

- Blastemal regions have significantly fewer CD4, CD8, and CD206 immune cells compared to mesenchymal regions.
- CD206, CD86, and CD68 immune cell abundance in blastemal and mesenchymal regions is significantly associated with prognosis and relapse timing.
- Region-specific immune profiling could improve risk stratification for intermediate-risk Wilms tumor patients.

## Abstract

Wilms tumor (WT) is characterized by a unique ternary histology, including blastemal, epithelial, and mesenchymal elements. Although overall survival is high, relapse and metastasis affect not only high-risk but also intermediate-risk (IR) patients. We here analyzed immune cell infiltrates in relation to histomorphological tumor regions of patients treated with neo-adjuvant chemotherapy and evaluated their role for disease prognosis. We included 46 chemotherapy-treated WTs resected between 2002 and 2020, which affected 27 females and 19 males at a median age of 35.58 months. Tumor samples were re-evaluated resulting in 13 mixed, 12 regressive, 8 blastemal, 7 mesenchymal, and 6 epithelial subtypes. HALO was used for automated quantification of the immunohistochemical stainings. Immune markers abundance was highly dependent on the histomorphological region. We observed significantly lower amounts of CD4, CD8, and CD206 positive immune cells in the blastemal region, as compared to the mesenchymal region. Moreover, abundance of CD206, CD86, and CD68 positive immune cells in the mesenchymal and blastemal regions showed a significant association with prognosis and timing of relapse. In conclusion, WT displays region-specific differences in immune cell infiltration. Evaluating CD206, CD86, and CD68 expression in mesenchymal and blastemal regions might be valuable for improving IR patient stratification.

Wilms tumors show distinct immune microenvironments across histological regions. In 46 treated cases, HALO-based quantification revealed reduced immune infiltration in blastemal areas and prognostic relevance of CD206, CD86, and CD68 in blastemal and mesenchymal regions. Region-specific immune profiling can improve risk stratification beyond current histological classification.