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

Publication ,  Journal Article
Garber, ST; Hashimoto, Y; Weathers, S-P; Xiu, J; Gatalica, Z; Verhaak, RGW; Zhou, S; Fuller, GN; Khasraw, M; de Groot, J; Reddy, SK ...
Published in: Neuro Oncol
October 2016

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.

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Published In

Neuro Oncol

DOI

EISSN

1523-5866

Publication Date

October 2016

Volume

18

Issue

10

Start / End Page

1357 / 1366

Location

England

Related Subject Headings

  • Young Adult
  • Programmed Cell Death 1 Receptor
  • Oncology & Carcinogenesis
  • Mutation
  • Middle Aged
  • Male
  • Lymphocytes, Tumor-Infiltrating
  • In Situ Hybridization, Fluorescence
  • Immunohistochemistry
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Garber, S. T., Hashimoto, Y., Weathers, S.-P., Xiu, J., Gatalica, Z., Verhaak, R. G. W., … Heimberger, A. B. (2016). Immune checkpoint blockade as a potential therapeutic target: surveying CNS malignancies. Neuro Oncol, 18(10), 1357–1366. https://doi.org/10.1093/neuonc/now132
Garber, Sarah T., Yuuri Hashimoto, Shiao-Pei Weathers, Joanne Xiu, Zoran Gatalica, Roel G. W. Verhaak, Shouhao Zhou, et al. “Immune checkpoint blockade as a potential therapeutic target: surveying CNS malignancies.Neuro Oncol 18, no. 10 (October 2016): 1357–66. https://doi.org/10.1093/neuonc/now132.
Garber ST, Hashimoto Y, Weathers S-P, Xiu J, Gatalica Z, Verhaak RGW, et al. Immune checkpoint blockade as a potential therapeutic target: surveying CNS malignancies. Neuro Oncol. 2016 Oct;18(10):1357–66.
Garber, Sarah T., et al. “Immune checkpoint blockade as a potential therapeutic target: surveying CNS malignancies.Neuro Oncol, vol. 18, no. 10, Oct. 2016, pp. 1357–66. Pubmed, doi:10.1093/neuonc/now132.
Garber ST, Hashimoto Y, Weathers S-P, Xiu J, Gatalica Z, Verhaak RGW, Zhou S, Fuller GN, Khasraw M, de Groot J, Reddy SK, Spetzler D, Heimberger AB. Immune checkpoint blockade as a potential therapeutic target: surveying CNS malignancies. Neuro Oncol. 2016 Oct;18(10):1357–1366.
Journal cover image

Published In

Neuro Oncol

DOI

EISSN

1523-5866

Publication Date

October 2016

Volume

18

Issue

10

Start / End Page

1357 / 1366

Location

England

Related Subject Headings

  • Young Adult
  • Programmed Cell Death 1 Receptor
  • Oncology & Carcinogenesis
  • Mutation
  • Middle Aged
  • Male
  • Lymphocytes, Tumor-Infiltrating
  • In Situ Hybridization, Fluorescence
  • Immunohistochemistry
  • Humans