PD‐L1 regulates tumor proliferation and T‐cell function in NF2‐associated meningiomas

作者：Ying Wang, Chao Zhang, Minjun Yan, Xin Ma, Lairong Song, Bo Wang, Peng Li, Pinan Liu · 发表于：CNS Neuroscience & Therapeutics · 年份：2024 · DOI：10.1111/cns.14784 · 被引用次数：11 · 研究领域：Meningioma and schwannoma management、Neurofibromatosis and Schwannoma Cases、Brain Metastases and Treatment

Abstract Introduction Programmed death‐ligand 1 (PD‐L1) expression is an immune evasion mechanism that has been demonstrated in many tumors and is commonly associated with a poor prognosis. Over the years, anti‐PD‐L1 agents have gained attention as novel anticancer therapeutics that induce durable tumor regression in numerous malignancies. They may be a new treatment choice for neurofibromatosis type 2 (NF2) patients. Aims The aims of this study were to detect the expression of PD‐L1 in NF2‐associated meningiomas, explore the effect of PD‐L1 downregulation on tumor cell characteristics and T‐cell functions, and investigate the possible pathways that regulate PD‐L1 expression to further dissect the possible mechanism of immune suppression in NF2 tumors and to provide new treatment options for NF2 patients. Results PD‐L1 is heterogeneously expressed in NF2‐associated meningiomas. After PD‐L1 knockdown in NF2‐associated meningioma cells, tumor cell proliferation was significantly inhibited, and the apoptosis rate was elevated. When T cells were cocultured with siPD‐L1‐transfected NF2‐associated meningioma cells, the expression of CD69 on both CD4 + and CD8 + T cells was partly reversed, and the capacity of CD8 + T cells to kill siPD‐L1‐transfected tumor cells was partly restored. Results also showed that the PI3K–AKT–mTOR pathway regulates PD‐L1 expression, and the mTOR inhibitor rapamycin rapidly and persistently suppresses PD‐L1 expression. In vivo experimental results suggest...