Deakin University
Browse

Immune checkpoint blockade as a potential therapeutic target: surveying CNS malignancies

Download (836.85 kB)
Version 2 2024-06-04, 08:45
Version 1 2018-06-12, 09:47
journal contribution
posted on 2024-06-04, 08:45 authored by ST Garber, Y Hashimoto, S-P Weathers, J Xiu, Z Gatalica, RGW Verhaak, S Zhou, GN Fuller, M Khasraw, J de Groot, SK Reddy, D Spetzler, AB Heimberger
BACKGROUND: Expression of programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) across glioma grades is undocumented, and their interactions with commonly expressed genetic and epigenetic alterations are undefined but nonetheless highly relevant to combinatorial treatments. METHODS: Patients with CNS malignancies were profiled by Caris Life Sciences from 2009 to 2016. Immunohistochemistry findings for PD-1 on tumor-infiltrating lymphocytes (TIL) and PD-L1 on tumor cells were available for 347 cases. Next-generation sequencing, pyrosequencing, immunohistochemistry, fragment analysis, and fluorescence in situ hybridization were used to determine isocitrate dehydrogenase 1 (IDH1), phosphatase and tensin homolog (PTEN), and tumor protein 53 mutational status, O(6)-DNA methylguanine-methyltransferase promoter methylation (MGMT-Me) status, PTEN expression, plus epidermal growth factor receptor variant III and 1p/19q codeletion status. RESULTS: PD-1+ TIL expression and grade IV gliomas were significantly positively correlated (odds ratio [OR]: 6.363; 95% CI: 1.263, 96.236)-especially in gliosarcomas compared with glioblastoma multiforme (P = .014). PD-L1 expression was significantly correlated with tumor grade with all PD-L1+ cases (n = 21) being associated with grade IV gliomas. PD-1+ TIL expression and PD-L1 expression were significantly correlated (OR: 5.209; 95% CI: 1.555, 20.144). Mutations of PTEN, tumor protein 53, BRAF, IDH1, and epidermal growth factor receptor or MGMT-Me did not associate with increased intratumoral expression of either PD-1+ TIL or PD-L1 in glioblastoma multiforme even before false discovery rate correction for multiple comparison. CONCLUSIONS: Targeting immune checkpoints in combination with other therapeutics based on positive biomarker selection will require screening of large patient cohorts.

History

Journal

Neuro-oncology

Volume

18

Pagination

1357-1366

Location

Oxford, Eng.

Open access

  • Yes

eISSN

1523-5866

Language

eng

Publication classification

C Journal article, C1.1 Refereed article in a scholarly journal

Copyright notice

2016, The Authors

Issue

10

Publisher

Oxford University Press