ArticlePediatric blood & cancer2025
PD-L1 Expression is Mediated by microRNA Processing, Wnt/β-Catenin Signaling, and Chemotherapy in Wilms Tumor.
Article in Pediatric blood & cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Abstract
backgroundInhibition of immune checkpoint proteins is effective in adult cancers but has shown limited efficacy in pediatric cancers. While factors regulating expression of immune checkpoint proteins such as PD-L1 are well documented in adult cancers, their regulation is poorly understood in pediatric cancers.
methodsWe analyzed Wilms tumor specimens with reverse-phase protein arrays. We validated correlations using published sequencing data, flow cytometry, and immunoblots.
resultsUsing unsupervised clustering of protein arrays, we found that immune markers like PD-L1 are upregulated in distinct subsets of Wilms tumor, the most common pediatric kidney cancer. Specifically, chemotherapy-exposed Wilms tumor specimens exhibited higher levels of PD-L1 expression, and common chemotherapeutics upregulated PD-L1 in vitro. Furthermore, mutations in CTNNB1 and DROSHA, the two most commonly mutated genes in Wilms tumor, correlated with higher PD-L1. Activation of Wnt/β-catenin signaling and knockdown of DROSHA or DICER1 both increase PD-L1 in vitro.
conclusionsTogether, our results identify clinical and biological properties regulating PD-L1 in Wilms tumor that may inform precision therapy approaches in pediatric immuno-oncology.
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