TY - JOUR
T1 - Molecular subgroups and B7-H4 expression levels predict responses to dendritic cell vaccines in glioblastoma
T2 - an exploratory randomized phase II clinical trial
AU - Yao, Yu
AU - Luo, Feifei
AU - Tang, Chao
AU - Chen, Dikang
AU - Qin, Zhiyong
AU - Hua, Wei
AU - Xu, Ming
AU - Zhong, Ping
AU - Yu, Shuangquan
AU - Chen, Di
AU - Ding, Xiaojie
AU - Zhang, Yi
AU - Zheng, Xiujuan
AU - Yang, Jiao
AU - Qian, Jiawen
AU - Deng, Yuting
AU - Hoon, Dave S.B.
AU - Hu, Jian
AU - Chu, Yiwei
AU - Zhou, Liangfu
N1 - Funding Information:
Funding This work was supported by the National Natural Science Foundation of China Grants (81472347 to Liangfu Zhou, 81572478, 81372708 to Yu Yao, 81772672 to Chao Tang, 31400772 to Feifei Luo, 31570892 to Yiwei Chu); and the Science and Technology Commission of Shanghai Municipality Grants (13JC1408000 to Liangfu Zhou, 13JC1407700 to Yiwei Chu).
Publisher Copyright:
© 2018, Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2018/11/1
Y1 - 2018/11/1
N2 - 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 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.
AB - 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 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.
KW - Active-specific immunotherapy
KW - B7-H4
KW - Dendritic cell vaccine
KW - Glioblastoma multiforme
KW - IDH
KW - TERT
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U2 - 10.1007/s00262-018-2232-y
DO - 10.1007/s00262-018-2232-y
M3 - Article
C2 - 30159779
AN - SCOPUS:85052695119
SN - 0340-7004
VL - 67
SP - 1777
EP - 1788
JO - Cancer Immunology, Immunotherapy
JF - Cancer Immunology, Immunotherapy
IS - 11
ER -