title: Immune checkpoint blockade as a potential therapeutic target: surveying CNS malignancies.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Targeting immune checkpoints in combination with other therapeutics based on positive biomarker selection will require screening of large patient cohorts.
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (S.T.G., Y.H., A.B.H.); Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (S.-P.W., J.d.G.); Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (R.G.W.V.); Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (S.Z.); Department of Neuropathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (G.N.F.); Caris Life Sciences, Phoenix, Arizona, USA (J.X., Z.G., S.K.R., D.S.); The University of Sydney, Sydney, Australia (M.K.).
authors.forename: Sarah T
authors.initials: ST
authors.lastname: Garber
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (S.T.G., Y.H., A.B.H.); Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (S.-P.W., J.d.G.); Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (R.G.W.V.); Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (S.Z.); Department of Neuropathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (G.N.F.); Caris Life Sciences, Phoenix, Arizona, USA (J.X., Z.G., S.K.R., D.S.); The University of Sydney, Sydney, Australia (M.K.).
authors.forename: Yuuri
authors.initials: Y
authors.lastname: Hashimoto
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (S.T.G., Y.H., A.B.H.); Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (S.-P.W., J.d.G.); Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (R.G.W.V.); Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (S.Z.); Department of Neuropathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (G.N.F.); Caris Life Sciences, Phoenix, Arizona, USA (J.X., Z.G., S.K.R., D.S.); The University of Sydney, Sydney, Australia (M.K.).
authors.forename: Shiao-Pei
authors.initials: SP
authors.lastname: Weathers
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (S.T.G., Y.H., A.B.H.); Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (S.-P.W., J.d.G.); Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (R.G.W.V.); Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (S.Z.); Department of Neuropathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (G.N.F.); Caris Life Sciences, Phoenix, Arizona, USA (J.X., Z.G., S.K.R., D.S.); The University of Sydney, Sydney, Australia (M.K.).
authors.forename: Joanne
authors.initials: J
authors.lastname: Xiu
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (S.T.G., Y.H., A.B.H.); Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (S.-P.W., J.d.G.); Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (R.G.W.V.); Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (S.Z.); Department of Neuropathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (G.N.F.); Caris Life Sciences, Phoenix, Arizona, USA (J.X., Z.G., S.K.R., D.S.); The University of Sydney, Sydney, Australia (M.K.).
authors.forename: Zoran
authors.initials: Z
authors.lastname: Gatalica
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (S.T.G., Y.H., A.B.H.); Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (S.-P.W., J.d.G.); Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (R.G.W.V.); Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (S.Z.); Department of Neuropathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (G.N.F.); Caris Life Sciences, Phoenix, Arizona, USA (J.X., Z.G., S.K.R., D.S.); The University of Sydney, Sydney, Australia (M.K.).
authors.forename: Roel G W
authors.initials: RG
authors.lastname: Verhaak
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (S.T.G., Y.H., A.B.H.); Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (S.-P.W., J.d.G.); Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (R.G.W.V.); Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (S.Z.); Department of Neuropathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (G.N.F.); Caris Life Sciences, Phoenix, Arizona, USA (J.X., Z.G., S.K.R., D.S.); The University of Sydney, Sydney, Australia (M.K.).
authors.forename: Shouhao
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (S.T.G., Y.H., A.B.H.); Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (S.-P.W., J.d.G.); Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (R.G.W.V.); Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (S.Z.); Department of Neuropathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (G.N.F.); Caris Life Sciences, Phoenix, Arizona, USA (J.X., Z.G., S.K.R., D.S.); The University of Sydney, Sydney, Australia (M.K.).
authors.forename: Gregory N
authors.initials: GN
authors.lastname: Fuller
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (S.T.G., Y.H., A.B.H.); Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (S.-P.W., J.d.G.); Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (R.G.W.V.); Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (S.Z.); Department of Neuropathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (G.N.F.); Caris Life Sciences, Phoenix, Arizona, USA (J.X., Z.G., S.K.R., D.S.); The University of Sydney, Sydney, Australia (M.K.).
authors.forename: Mustafa
authors.initials: M
authors.lastname: Khasraw
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (S.T.G., Y.H., A.B.H.); Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (S.-P.W., J.d.G.); Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (R.G.W.V.); Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (S.Z.); Department of Neuropathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (G.N.F.); Caris Life Sciences, Phoenix, Arizona, USA (J.X., Z.G., S.K.R., D.S.); The University of Sydney, Sydney, Australia (M.K.).
authors.forename: John
authors.initials: J
authors.lastname: de Groot
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (S.T.G., Y.H., A.B.H.); Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (S.-P.W., J.d.G.); Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (R.G.W.V.); Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (S.Z.); Department of Neuropathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (G.N.F.); Caris Life Sciences, Phoenix, Arizona, USA (J.X., Z.G., S.K.R., D.S.); The University of Sydney, Sydney, Australia (M.K.).
authors.forename: Sandeep K
authors.initials: SK
authors.lastname: Reddy
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (S.T.G., Y.H., A.B.H.); Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (S.-P.W., J.d.G.); Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (R.G.W.V.); Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (S.Z.); Department of Neuropathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (G.N.F.); Caris Life Sciences, Phoenix, Arizona, USA (J.X., Z.G., S.K.R., D.S.); The University of Sydney, Sydney, Australia (M.K.).
authors.forename: David
authors.initials: D
authors.lastname: Spetzler
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (S.T.G., Y.H., A.B.H.); Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (S.-P.W., J.d.G.); Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (R.G.W.V.); Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (S.Z.); Department of Neuropathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (G.N.F.); Caris Life Sciences, Phoenix, Arizona, USA (J.X., Z.G., S.K.R., D.S.); The University of Sydney, Sydney, Australia (M.K.) aheimber@mdanderson.org.
authors.forename: Amy B
authors.initials: AB
authors.lastname: Heimberger
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060890:B7-H1 Antigen / Q000032:analysis / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D061026:Programmed Cell Death 1 Receptor / Q000032:analysis / Q000096:biosynthesis*; D055815:Young Adult
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
keywords: PD-1; PD-L1; glioblastoma; immune checkpoint; low-grade glioma