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Over the years, anti\u2010PD\u2010L1 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>The aims of this study were to detect the expression of PD\u2010L1 in NF2\u2010associated meningiomas, explore the effect of PD\u2010L1 downregulation on tumor cell characteristics and T\u2010cell functions, and investigate the possible pathways that regulate PD\u2010L1 expression to further dissect the possible mechanism of immune suppression in NF2 tumors and to provide new treatment options for NF2 patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>PD\u2010L1 is heterogeneously expressed in NF2\u2010associated meningiomas. After PD\u2010L1 knockdown in NF2\u2010associated meningioma cells, tumor cell proliferation was significantly inhibited, and the apoptosis rate was elevated. When T cells were cocultured with siPD\u2010L1\u2010transfected NF2\u2010associated meningioma cells, the expression of CD69 on both CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T cells was partly reversed, and the capacity of CD8<jats:sup>+<\/jats:sup> T cells to kill siPD\u2010L1\u2010transfected tumor cells was partly restored. Results also showed that the PI3K\u2013AKT\u2013mTOR pathway regulates PD\u2010L1 expression, and the mTOR inhibitor rapamycin rapidly and persistently suppresses PD\u2010L1 expression. In\u00a0vivo experimental results suggested that anti\u2010PD\u2010L1 antibody may have a synergetic effect with the mTOR inhibitor in reducing tumor cell proliferation and that reduced PD\u2010L1 expression could contribute to antitumor efficacy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Targeting PD\u2010L1 could be helpful for restoring the function of tumor\u2010infiltrating lymphocytes and inducing apoptosis to inhibit tumor proliferation in NF2\u2010associated meningiomas. Dissecting the mechanisms of the PD\u2010L1\u2010driven tumorigenesis of NF2\u2010associated meningioma will help to improve our understanding of the mechanisms underlying tumor progression and could facilitate further refinement of current therapies to improve the treatment of NF2 patients.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.14784","type":"journal-article","created":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T09:39:37Z","timestamp":1717407577000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["PD\u2010L1 regulates tumor proliferation and T\u2010cell function in NF2\u2010associated meningiomas"],"prefix":"10.1111","volume":"30","author":[{"given":"Ying","family":"Wang","sequence":"first","affiliation":[{"name":"Beijing Neurosurgical Institute Capital Medical University  Beijing China"},{"name":"Department of Neurosurgery, Beijing Tiantan Hospital Capital Medical University  Beijing 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