Molecular subgroups and B7-H4 expression levels predict responses to dendritic cell vaccines in glioblastoma: an exploratory randomized phase II clinical trial.
Cancer Immunol Immunother
; 67(11): 1777-1788, 2018 Nov.
Article
in En
| MEDLINE
| ID: mdl-30159779
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 11 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 IDH1wild type (WT) TERTMT patients, DCV treatment significantly prolonged OS (p < 0.01) and PFS (p = 0.03) and increased plasma levels of cytokines CCL22 and IFN-γ compared with placebo. Patients with low B7-H4 expression showed significantly prolonged OS (p = 0.02) after DCV treatment. Therefore, IDH1WTTERTMT and low B7-H4 expression identified subgroups of GBM patients more responsive to GSC DCV-based specific active-immunotherapy.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Dendritic Cells
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Biomarkers, Tumor
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Glioblastoma
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Cancer Vaccines
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V-Set Domain-Containing T-Cell Activation Inhibitor 1
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Mutation
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Neoplasm Recurrence, Local
Type of study:
Clinical_trials
/
Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Limits:
Adolescent
/
Adult
/
Aged
/
Female
/
Humans
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Male
/
Middle aged
Language:
En
Journal:
Cancer Immunol Immunother
Journal subject:
ALERGIA E IMUNOLOGIA
/
NEOPLASIAS
/
TERAPEUTICA
Year:
2018
Type:
Article
Affiliation country:
China