EV PD-L1 Contributes to Immunosuppressive CD8⁺ T Cells in Peripheral Blood of Pediatric Wilms Tumor

Abstract

Wilms tumor (WT) is the most common renal cancer and the most prevalent abdominal cancer in children. Children with recurrent or progressive forms of WT could benefit from novel immune-targeted approaches. While the immune status of these patients, especially the immunosuppression of peripheral T cells, was rarely reported. The present study enrolled a consecutive series of 14 Chinese WT children and 14 age- and gender-matched healthy controls. We demonstrated that plasma extracellular vesicular (EV) PD-L1 levels significantly increased in WT patients than in healthy controls. EV PD-L1 significantly inhibited the activation of human CD8+ T cells by down-regulating the cell surface CD69 expression and the intracellular IFNγ and TNFα production in vitro. In peripheral CD8+ T cells of WT patients, the intracellular IFNγ and TNFα production significantly decreased than healthy controls. The level of plasma EV PD-L1 significantly correlated with the intracellular TNFα production in peripheral CD8+ T cells of WT patients. In conclusion, the significantly increased plasma EV PD-L1 in WT patients contributed to the immunosuppression of peripheral CD8+ T cells. Monitoring the level of plasma EV PD-L1 will be helpful for the selection of immune-targeted therapies for WT patients.

DNA Hypermethylation-Regulated CX3CL1 Reducing T Cell Infiltration Indicates Poor Prognosis in Wilms Tumour

“…But there are few reports of childhood tumours. Previous studies have shown that a significant increase in plasma EV PD-L1 in WT patients contributes to the immunosuppression of peripheral CD8+ T cells (23). This suggests that nephroblastoma also has immunosuppression similar to that in adult tumors.…”

Extracellular vesicles in kidney development and pediatric kidney diseases

“…In Wilms tumor, however, a single study focused on the analysis of EV-expressed immune checkpoint molecule PD-L1 as a Wilms tumor progression marker. When evaluating PD-L1 levels on plasma EVs from fourteen Wilms tumor patients [ 24 ], PD-L1 appeared significantly correlated with CD8 + T cell function inhibition. However, the study has weak spots; for example, no change was observed in some of the effector T cell markers when T cells were co-cultured with PD-L1 EVs of patients, and no correlation between those markers and PD-L1 was observed.…”