Molecular subgroups and B7-H4 expression levels predict responses to dendritic cell vaccines in glioblastoma: an exploratory randomized phase II clinical trial
Molecular subgroups and B7-H4 expression levels predict responses to dendritic cell vaccines in glioblastoma: an exploratory randomized phase II clinical trial
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分子亚组和 B7-H4 表达水平预测胶质母细胞瘤树突状细胞疫苗的反应：一项探索性随机 II 期临床试验
DOI：
10.1007/s00262-018-2232-y
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发表时间：
2018-08
期刊：
影响因子：
--
通讯作者：
Liangfu Zhou
中科院分区：
文献类型：
--
作者：
Yu Yao;Feifei Luo;Chao Tang;Dikang Chen;Zhiyong Qin;Wei Hua;Ming Xu;Ping Zhong;Shuangquan Yu;Di Chen;Xiaojie Ding;Yi Zhang;Xiujuan Zheng;Jiao Yang;Jiawen Qian;Yuting Deng;Dave S B Hoon;Jian Hu;Yiwei Chu;Liangfu Zhou
基于树突状细胞（DC）的疫苗接种是用于主动特异性免疫治疗的有前途的方法，但目前效力有限。在多形性胶质母细胞瘤（GBM）患者中评估了负载胶质母细胞瘤干细胞样（GSC）抗原的DC疫苗（DCV）的安全性和有效性。在这项双盲、安慰剂对照的II期临床试验中，43名GBM患者在手术后以1：1的比例随机接受DCV（n= 22）或生理盐水安慰剂（n= 21）。分析总生存期（OS）和无进展生存期（PFS）。根据异柠檬酸脱氢酶（IDH 1/2）和端粒酶逆转录酶（TERT）的突变（MT）状态，将参与者分为不同的分子亚组。还评估了血浆细胞因子水平、肿瘤浸润淋巴细胞数量和免疫共抑制分子PD-L1和B7-H4。多变量考克斯回归分析显示，在调整IDH 1和TERT启动子MT和B7-H4表达后，DCV治疗显著延长了OS（p= 0.02），原发性与复发性GBM。在IDH 1野生型（WT）TERTMT患者中，与安慰剂相比，DCV治疗显著延长OS（p< 0.01）和PFS（p= 0.03），并增加细胞因子CCL 22和IFN-γ的血浆水平。B7-H4低表达的患者在DCV治疗后显示OS显著延长（p= 0.02）。因此，IDH 1 WTTERTMT和低B7-H4表达确定了GBM患者亚组对基于GSC DCV的特异性主动免疫疗法更有反应。
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)TERTMTpatients, 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, IDH1WTTERTMTand low B7-H4 expression identified subgroups of GBM patients more responsive to GSC DCV-based specific active-immunotherapy.
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影响因子：
158.5
作者：
Stupp, R;Mason, WP;Ryan, G
通讯作者：
Ryan, G
TERT 启动子突变导致 IDH 突变，从而预测 WHO II 级和 III 级弥漫性胶质瘤对辅助治疗的差异反应。
影响因子：
--
作者：
Zhang ZY;Chan AK;Ding XJ;Qin ZY;Hong CS;Chen LC;Zhang X;Zhao FP;Wang Y;Wang Y;Zhou LF;Zhuang Z;Ng HK;Yan H;Yao Y;Mao Y
通讯作者：
Mao Y
DOI：
10.1056/nejmoa1407279
发表时间：
2015-06-25
期刊：
The New England journal of medicine
影响因子：
--
作者：
Eckel-Passow JE;Lachance DH;Molinaro AM;Walsh KM;Decker PA;Sicotte H;Pekmezci M;Rice T;Kosel ML;Smirnov IV;Sarkar G;Caron AA;Kollmeyer TM;Praska CE;Chada AR;Halder C;Hansen HM;McCoy LS;Bracci PM;Marshall R;Zheng S;Reis GF;Pico AR;O'Neill BP;Buckner JC;Giannini C;Huse JT;Perry A;Tihan T;Berger MS;Chang SM;Prados MD;Wiemels J;Wiencke JK;Wrensch MR;Jenkins RB
通讯作者：
Jenkins RB
DOI：
10.1038/nrc3258
发表时间：
2012-03-22
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1016/s0513-5117(10)79301-7
发表时间：
2010
期刊：
Yearbook of Neurology and Neurosurgery
影响因子：
--
作者：
J. Uhm
通讯作者：
J. Uhm