EV PD-L1 与临床特征相关，并有助于抑制小儿甲状腺癌中的 T 细胞。

EV PD-L1 is Correlated With Clinical Features and Contributes to T Cell Suppression in Pediatric Thyroid Cancer.

机构信息

Beijing Children's Hospital, Capital Medical University, National Center for Children's Health (NCCH), Beijing, China.

Department of Pathology, Beijing Children's Hospital, Capital Medical University, Beijing, China.

出版信息

J Clin Endocrinol Metab. 2020 Aug 1;105(8). doi: 10.1210/clinem/dgaa309.

DOI:10.1210/clinem/dgaa309

PMID:32459310

Abstract

CONTEXT

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.

OBJECTIVE

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.

MAIN OUTCOME MEASURES

Plasma levels of EV and soluble PD-L1 and PD-1 and levels of plasma cytokines in children with PTC and controls were determined by enzyme-linked immunosorbent assay. 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 tumor necrosis factor-α (TNFα) and interferon-γ (IFNγ) secretion were measured by flow cytometry.

RESULTS

The levels of plasma PD-L1/PD-1 were significantly higher in children with PTC 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.

CONCLUSIONS

Plasma levels of EV PD-L1, but not soluble PD-L1, were associated with tumor T stage in children with PTC. Plasma EV PD-L1 emerges as a useful metric for assessing tumor T stage and T cell suppression in PTC.

摘要

背景

血液细胞外囊泡程序性死亡配体 1（PD-L1）和程序性死亡受体 1（PD-1）在甲状腺乳头状癌（PTC）中的作用尚不确定。

目的

我们旨在确定 EV PD-L1/PD-1与儿童 PTC 临床特征的关系以及 EV PD-L1 在免疫抑制中的作用。

主要观察指标

通过酶联免疫吸附试验测定儿童 PTC 患者和对照组的血浆 EV 和可溶性 PD-L1、PD-1 水平以及血浆细胞因子水平。通过免疫组织化学测定肿瘤 PD-L1 和肿瘤浸润淋巴细胞（TIL）评分。分析血浆 PD-L1/PD-1 水平与临床病理特征、血浆细胞因子水平、肿瘤 PD-L1 表达和 TIL 评分的相关性。通过将 PD-L1 高或 PD-L1 低 EV 与激活的 CD8+T 细胞孵育，测定来自 PTC 患者的 EV 对 T 细胞的抑制作用。通过流式细胞术测定 CD69 和 PD-1 表达的变化以及肿瘤坏死因子-α（TNFα）和干扰素-γ（IFNγ）分泌的变化。

结果

与对照组相比，儿童 PTC 患者的血浆 PD-L1/PD-1 水平明显升高。血浆 EV PD-L1 水平与肿瘤 T 分期、肿瘤 PD-L1 表达、TIL 评分和血浆细胞因子含量显著相关。血浆可溶性 PD-1 水平与患者年龄、血浆 EV PD-L1 和 IFNα浓度显著相关。PD-L1 高 EV 显著抑制 CD8+T 细胞的激活。