Immune Expression in Children with Wilms Tumor
Ashley W. Johnston, MD, Jonathan C. Routh, MD, MPH, Smita K. Nair, PhD, Eda K. Holl, PhD
BACKGROUND: Due to improvements in multimodality therapy over the last several decades, survival among children with Wilms tumor (WT) now exceeds 90%. However, up to 15% of children with favorable WT and up to 50% of children with anaplastic WT will experience tumor recurrence or progression. Survival for these children is dramatically reduced; only 50% survive to adulthood. In adult renal tumors, immune manipulation has been effective at improving survival. However, little is known regarding the immune milieu of WT.
METHODS: Between 2016 and 2017, we performed a pilot study wherein children with WT underwent ex vivo wedge biopsy following their nephrectomy. Fresh tumor tissue and serum were then enzymatically digested to analyze the tumor infiltrating immune infiltrate using flow cytometry. Immune analysis was then conducted using a panel for tumor infiltrating and effector cells. Immunohistochemistry was also performed for CD4, CD8, and PD-L1 expression.
RESULTS: A total of 5 patients were included (mean age 3.5 years, 3 females/2 males); 2 with unilateral WT (resected prior to chemotherapy), 2 with bilateral WT (resected after neoadjuvant chemotherapy), and one patient with Denys-Drash syndrome, end-stage renal disease, and a distant history of WT in the contralateral kidney enrolled as a "normal" control. Immune analysis showed that WT were infiltrated by immune cells prior to and following chemotherapy (Figure 1). There were elevated levels of NK cells infiltrating the tumor specimens; these were higher compared to levels of NK cells circulating in the blood (41 vs. 7%). T cells, mostly of CD8 origin, were also a major cell type in tumors (50.4%). These displayed an activated cell phenotype (Figure 2). Unlike the predominantly alpha-beta TCR T cells found in the blood, 33% of the T cells infiltrating the tumors were positive for TCR gamma-delta receptors.
CONCLUSIONS: These pilot data suggest an inflammatory tumor microenvironment is present within WT, implying that they may be susceptible to immunotherapy similar to adult renal tumors and other adult malignancies. Follow-up studies are currently underway.
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