Programmed death ligand 1 in meningioma [Neurosurgery Wiki]

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====== Programmed death ligand 1 in meningioma ======

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.

The aim of a study of Wang et al. was 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.

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 suggested that anti-PD-L1 antibody may have a synergetic effect with the mTOR inhibitor in reducing tumor cell proliferation and that reduced PD-L1 expression could contribute to antitumor efficacy.

Targeting PD-L1 could be helpful for restoring the function of tumor-infiltrating lymphocytes and inducing apoptosis to inhibit tumor proliferation in NF2-associated meningiomas. Dissecting the mechanisms of the PD-L1-driven tumorigenesis of NF2-associated 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
((Wang Y, Zhang C, Yan M, Ma X, Song L, Wang B, Li P, Liu P. PD-L1 regulates tumor proliferation and T-cell function in NF2-associated meningiomas. CNS Neurosci Ther. 2024 Jun;30(6):e14784. doi: 10.1111/cns.14784. PMID: 38828669.)).
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It is upregulated in aggressive meningiomas
((Bi WL, Nayak L, Meredith DM, Driver J, Du Z, Hoffman S, Li Y, Lee EQ, Beroukhim R, Rinne M, McFaline-Figueroa R, Chukwueke U, McCluskey C, Gaffey S, Cherniack AD, Stefanik J, Doherty L, Taubert C, Cifrino M, LaFrankie D, Graillon T, Wen PY, Ligon KL, Al-Mefty O, Huang RY, Muzikansky A, Chiocca EA, Santagata S, Dunn IF, Reardon DA. Activity of [[PD-1]] blockade with [[Nivolumab]] among patients with recurrent atypical/[[anaplastic meningioma]]: Phase II [[trial]] results. Neuro Oncol. 2021 May 20:noab118. doi: 10.1093/neuonc/noab118. Epub ahead of print. PMID: 34015129.))