Immune response in patients with newly diagnosed glioblastoma multiforme treated with intranodal autologous tumor lysate-dendritic cell vaccination after radiation chemotherapy.
Immune response in patients with newly diagnosed glioblastoma multiforme treated with intranodal autologous tumor lysate-dendritic cell vaccination after radiation chemotherapy.
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新诊断的多形性胶质母细胞瘤患者在放射化疗后接受结内自体肿瘤裂解物-树突状细胞疫苗接种治疗的免疫反应。
DOI：
10.1097/cji.0b013e318215e300
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发表时间：
2011-05
期刊：
影响因子：
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通讯作者：
Ernstoff MS
中科院分区：
文献类型：
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作者：
Fadul CE;Fisher JL;Hampton TH;Lallana EC;Li Z;Gui J;Szczepiorkowski ZM;Tosteson TD;Rhodes CH;Wishart HA;Lewis LD;Ernstoff MS
多形性胶质母细胞瘤（GBM）患者的免疫功能受到严重抑制，在常规放射治疗和替莫唑胺（TMZ）联合治疗下，抗肿瘤免疫反应的恢复可能会使患者受益。评估临床相关免疫应答治疗的最佳策略尚未确定。本研究的主要目的是确定放射治疗和TMZ后GBM患者对宫颈结内接种自体肿瘤裂解物负载树突状细胞（dc）的免疫反应。我们使用了一种新的分层聚类分析免疫参数测量前后接种疫苗。次要目的是评估治疗可行性，并将免疫反应与无进展生存期（PFS）和总生存期联系起来。10名符合条件的患者接受了疫苗接种。接种后测量的肿瘤特异性细胞毒性T细胞反应增强了CD4+ T和CD4+干扰素γ产生细胞的前体频率。多个功能结局的分层聚类分析根据患者的免疫反应区分出两组患者，另外显示至少一项免疫功能参数处于前五分之一的患者生存率提高。未发现与DC疫苗接种相关的严重不良事件。所有患者在诊断后6个月存活，6个月PFS为90%。中位PFS为9.5个月，总生存期为28个月。我们的数据表明，在GBM患者中，DC疫苗联合放疗和化疗是可行的，安全的，并且可能诱导肿瘤特异性免疫反应。
Patients with glioblastoma multiforme (GBM) are profoundly immunosuppressed and may benefit from restoration of an antitumor immune response in combination with conventional radiation therapy and temozolomide (TMZ). The optimal strategies to evaluate clinically relevant immune responses to treatment have yet to be determined. The primary objective of our study was to determine immunologic response to cervical intranodal vaccination with autologous tumor lysate-loaded dendritic cells (DCs) in patients with GBM after radiation therapy and TMZ. We used a novel hierarchical clustering analysis of immune parameters measured before and after vaccination. Secondary objectives were to assess treatment feasibility and to correlate immune response with progression-free survival (PFS) and overall survival. Ten eligible patients received vaccination. Tumor-specific cytotoxic T-cell response measured after vaccination was enhanced for the precursor frequency of CD4+ T and CD4+ interferon γ-producing cells. Hierarchical clustering analysis of multiple functional outcomes discerned 2 groups of patients according to their immune response, and additionally showed that patients in the top quintile for at least one immune function parameter had improved survival. There were no serious adverse events related to DC vaccination. All patients were alive at 6 months after diagnosis and the 6-month PFS was 90%. The median PFS was 9.5 months and overall survival was 28 months. In patients with GBM, immune therapy with DC vaccination after radiation and TMZ resulted in tumor-specific immune responses that were associated with prolonged survival. Our data suggest that DC vaccination in combination with radiation and chemotherapy in patients with GBM is feasible, safe, and may induce tumor-specific immune responses.