Csig-04. Immune Checkpoint Blockade as a Potential Therapeutic Target: Surveying Cns Malignancies
Year: 2016
Type: conference-abstract
Abstract: Expression of PD-1/PD-L1 across glioma grades is undocumented and their interactions with commonly expressed genetic and epigenetic alterations undefined but nonetheless highly relevant to combinatorial treatments. Patients with CNS malignancies were profiled by Caris Life Sciences from 2009-2016. Immunohistochemistry (IHC) findings for PD-1 on tumor-infiltrating lymphocytes (TIL) and PD-L1 on tumor cells were available for 347 cases. Next generation sequencing, pyrosequencing, IHC, fragment analysis, and fluorescence in situ hybridization (FISH) were used to determine IDH1, PTEN, and TP53 mutational status, MGMT promoter methylation (MGMT-Me) status, PTEN expression, plus epidermal growth factor receptor variant III (EGFRvIII) and 1p19q codeletion status. PD-1+ TIL expression and grade IV gliomas were significantly positively correlated (OR 6.363, 95% CI 1.263, 96.236) - especially in gliosarcomas compared with GBM (p = 0.014). PD-L1 expression was significantly correlated with tumor grade with all PD-L1 positive 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, TP53, BRAF, IDH1, and EGFR or MGMT-Me did not associate with increased intratumoral expression of either PD-1+ TIL or PD-L1 in GBM 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.
Source: Neuro-Oncology
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4243418873