Commentary to clinical significance of tumoral PD-L1 expression in wilms tumor

Published:December 09, 2021DOI:https://doi.org/10.1016/j.jpurol.2021.10.029
      The remarkable improvement in survival of children with Wilms tumor over the past half century rests on the combined use of surgery, chemotherapy and radiotherapy with risk stratified protocols, with risk stratification based on the independently prognostic variables of tumor stage and histology. Ninety percent of children with Wilms tumor now survive with the use of these risk-adapted treatment protocols, protocols which aim to achieve maximal survival with minimal short and long term toxicity of treatment. Yet ten percent of children still succumb to their cancer, most of whom will have presented with high risk disease (high stage, unfavorable histology) but a few of whom have initially presented with low risk disease (low stage, favorable histology). As our understanding of the genetic alterations which lead to the development and progression of Wilms tumor has grown [
      • Treger T.
      • Chowdhury T.
      • Pritchard-Jones K.
      • Behjati S.
      The genetic changes of Wilms tumor.
      ], there has been hope that biomarkers reflecting these alterations might lead to better risk stratifications and, importantly, targeted therapies that might further improve survival and lower toxicities. The article by Zhang et al. [

      Zhang L., Hui J., Miaomiao S., Wei L., Zhenxiang L., Jiamao L. Clinical significance of tumoral PD-L1 expression in Wilms tumor.

      ], and two earlier publications by Routh et al., (2008, 2013) [
      • Routh J.
      • Ashley R.
      • Sebo T.
      • Lohse C.
      • Husmann D.
      • Kramer S.
      • et al.
      B7-H1 expression in Wilms tumor: correlation with tumor biology and disease recurrence.
      ,
      • Routh J.
      • Grundt P.
      • Anderson J.
      • Retik A.
      • Kurek K.
      B7-H1 as a biomarker for failure in patients with favorable histology Wilms tumor.
      ] examine the biomarker PD-L1 (B7–H1) as a predictor of relapse and survival. PD-L1 (B7–H1) is normally expressed in macrophages, and aberrantly expressed in some tumors, where is appears to down regulate the host anti-tumor immune response. Agents that block the PD-L1 pathway have shown promise as anti tumor therapy [
      • Zou W.
      • Wolchok J.
      • Chen L.
      PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: mechanisms, response biomarkers and combinations.
      ]. PD-L1 was expressed in 28% of tumors in Zhangs's study and 14% and 65% of tumors respectively in the two studies by Routh, and correlated with higher stage, unfavorable histology, increased risk of relapse and poorer survival. However in none of these studies was PD-L1 expression independently predictive of relapse and/or decreased survival. This finding might be due to the small cohort size of these studies, and/or the lack of standardized techniques and evaluation of immunohistochemical staining, or might reflect the biology of the biomarker itself. There are no published studies at present evaluating PD-L1 as a therapeutic target in those Wilms tumors in which it is expressed. PD-L1 does not at present appear to have a role in the clinical management of patients with Wilms tumor but studies such as Zhange's are important steps in the search for risk factors defined by the tumor's molecular genetic profile in addition to those based on descriptive histologic staining characteristics.
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      References

      1. Zhang L., Hui J., Miaomiao S., Wei L., Zhenxiang L., Jiamao L. Clinical significance of tumoral PD-L1 expression in Wilms tumor.

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        Sci Transl Med. 2016; 8: 328v4

      Linked Article

      • Clinical significance of tumoral PD-L1 expression in Wilms tumors
        Journal of Pediatric Urology
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          Although cure rate for Wilms tumor (WT) is high recent years, there is still small fraction of patients suffering from tumor relapse or metastases. It is urgent to identify more valuable biomarkers associated with disease progression. Previous studies have shown that PD-L1 was abnormally expressed in various type of cancers and acted as predictor for poor prognosis for those cancers. PD-1/PD-L1 inhibitors have achieved great success in various malignancies with correlation between PD-L1 expression and responses.
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