Molecular subgroups and B7-H4 expression levels predict responses to dendritic cell vaccines in glioblastoma: an exploratory randomized phase II clinical trial.

Document Type

Article

Publication Date

8-22-2018

Publication Title

Cancer immunology, immunotherapy : CII

Keywords

Active-specific immunotherapy; B7-H4; Dendritic cell vaccine; Glioblastoma multiforme; IDH; TERT; Adolescent; Adult; Aged; Biomarkers, Tumor/genetics; Brain Neoplasms/genetics; Brain Neoplasms/immunology; Brain Neoplasms/pathology; Brain Neoplasms/therapy; Cancer Vaccines/therapeutic use; Combined Modality Therapy; Dendritic Cells/immunology; Double-Blind Method; Female; Follow-Up Studies; Glioblastoma/genetics; Glioblastoma/immunology; Glioblastoma/pathology; Glioblastoma/therapy; Humans; Isocitrate Dehydrogenase/genetics; Male; Middle Aged; Mutation; Neoplasm Recurrence, Local/genetics; Neoplasm Recurrence, Local/immunology; Neoplasm Recurrence, Local/pathology; Neoplasm Recurrence, Local/therapy; Prognosis; Promoter Regions, Genetic; Survival Rate; Telomerase/genetics; V-Set Domain-Containing T-Cell Activation Inhibitor 1/genetics; V-Set Domain-Containing T-Cell Activation Inhibitor 1/metabolism; Young Adult

Abstract

Dendritic cell (DC)-based vaccination is a promising approach for active-specific immunotherapy, but is currently of limited efficacy. The safety and effectiveness of a DC vaccine (DCV) loaded with glioblastoma stem cell-like (GSC) antigens was assessed in glioblastoma multiforme (GBM) patients. In this double-blind, placebo-controlled phase II clinical trial, 43 GBM patients were randomized after surgery at a 1:1 ratio to receive either DCV (n = 22) or normal saline placebo (n = 21). Overall survival (OS) and progression-free survival (PFS) were analysed. Participants were stratified into different molecular subgroups based on the mutation (MT) status of isocitrate dehydrogenase (IDH1/2) and telomerase reverse transcriptase (TERT). Plasma cytokine levels, tumor-infiltrating lymphocyte numbers and immune co-inhibitory molecules PD-L1 and B7-H4 were also assessed. Multivariate Cox regression analysis revealed that DCV treatment significantly prolonged OS (p = 0.02) after adjusting for IDH1 and TERT promoter MT and B7-H4 expression, primary vs recurrent GBM. Among IDH1

Clinical Institute

Cancer

Department

Oncology

Share

COinS