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Updated: Oct 20, 2025
Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
EV PD-L1 Contributes to Immunosuppressive CD8+ T Cells in Peripheral Blood of Pediatric Wilms Tumor
Xiaoxue Zhang1, Zongran Liu2, Yiran Hou3
1Xiang'an Hospital of Xiamen University, Xiamen, Fujian, China.
Insights
Increased plasma extracellular vesicular PD-L1 in children with Wilms tumor (WT) suppresses T cell function. Monitoring this biomarker may guide immune-targeted therapies for pediatric WT.
Area of Science:
- Pediatric Oncology
- Immunology
- Cancer Research
Background:
- Wilms tumor (WT) is the most common childhood renal cancer.
- Recurrent or progressive WT may benefit from immune-targeted therapies.
- The immune status, particularly T cell immunosuppression, in WT patients is understudied.
Purpose of the Study:
- To investigate the role of plasma extracellular vesicular (EV) PD-L1 in pediatric Wilms tumor.
- To assess the impact of EV PD-L1 on T cell function in WT patients.
- To explore EV PD-L1 as a potential biomarker for immune-targeted therapy selection.
Main Methods:
- Enrolled 14 Chinese children with WT and 14 age/gender-matched healthy controls.
- Quantified plasma extracellular vesicular (EV) PD-L1 levels.
- Assessed in vitro effects of EV PD-L1 on human CD8+ T cell activation (CD69, IFNγ, TNFα).
- Measured intracellular IFNγ and TNFα production in peripheral CD8+ T cells from WT patients.
Main Results:
- Plasma EV PD-L1 levels were significantly higher in WT patients compared to controls.
- EV PD-L1 inhibited CD8+ T cell activation, reducing CD69 expression and IFNγ/TNFα production.
- WT patients exhibited decreased intracellular IFNγ and TNFα in peripheral CD8+ T cells.
- Plasma EV PD-L1 levels correlated with reduced intracellular TNFα production in WT patients' CD8+ T cells.
Conclusions:
- Elevated plasma EV PD-L1 contributes to peripheral CD8+ T cell immunosuppression in Wilms tumor.
- Plasma EV PD-L1 is a potential biomarker for guiding immune-targeted therapy selection in pediatric WT.
- Further research into immune modulation in WT is warranted.
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.
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