EV PD-L1 is correlated with clinical features and contributes to T cell suppression in pediatric thyroid cancer.

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The contribution of blood extracellular vesicular (EV) programmed death-ligand 1 (PD-L1) and programmed death-1 (PD-1) in papillary thyroid cancer (PTC) is uncertain.We sought to determine the relationship of EV PD-L1/PD-1 with the clinical features of pediatric PTC and the role of EV PD-L1 in immunosuppression.Plasma levels of EV and soluble PD-L1 and PD-1 and levels of plasma cytokines in PTC children and controls were determined by ELISA. Levels of tumor PD-L1 and the tumor-infiltrating lymphocyte (TIL) score were determined by immunohistochemistry. Correlations of the plasma PD-L1/PD-1 level with clinicopathological characteristics, levels of plasma cytokines, tumor PD-L1 expression and TIL score were analyzed. T cell suppression by EVs from PTC patients was determined by incubation of PD-L1high or PD-L1low EVs with activated CD8+ T cells. Changes in CD69 and PD-1 expression and changes in TNFa and IFNγ secretion were measured by flow cytometry.The levels of plasma PD-L1/PD-1 were significantly higher in PTC children than in controls. The levels of plasma EV PD-L1 significantly correlated with tumor T stage, tumor PD-L1 expression, TIL score, and plasma cytokine content. Levels of plasma soluble PD-1 significantly correlated with patient age, plasma EV PD-L1 and IFNα concentration. PD-L1high EVs significantly inhibited the activation of CD8+ T cells.Plasma levels of EV PD-L1, but not soluble PD-L1, were associated with tumor T stage in PTC children. Plasma EV PD-L1 emerges as a useful metric for assessing tumor T stage and T cell suppression in PTC.

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