期刊
CANCER IMMUNOLOGY IMMUNOTHERAPY
卷 67, 期 11, 页码 1777-1788出版社
SPRINGER
DOI: 10.1007/s00262-018-2232-y
关键词
Dendritic cell vaccine; Glioblastoma multiforme; B7-H4; IDH; TERT; Active-specific immunotherapy
资金
- National Natural Science Foundation of China [81472347, 81572478, 81372708, 81772672, 31400772, 31570892]
- Science and Technology Commission of Shanghai Municipality Grants [13JC1408000, 13JC1407700]
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(wild 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- compared with placebo. Patients with low B7-H4 expression showed significantly prolonged OS (p=0.02) after DCV treatment. Therefore, IDH1(WT)TERT(MT) and low B7-H4 expression identified subgroups of GBM patients more responsive to GSC DCV-based specific active-immunotherapy.
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