TCR Sequencing Can Identify and Track Glioma-Infiltrating T Cells after DC Vaccination.
TCR Sequencing Can Identify and Track Glioma-Infiltrating T Cells after DC Vaccination.
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DOI：
10.1158/2326-6066.cir-15-0240
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发表时间：
2016-05
影响因子：
10.1
通讯作者：
Prins RM
中科院分区：
文献类型：
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作者：
Hsu M;Sedighim S;Wang T;Antonios JP;Everson RG;Tucker AM;Du L;Emerson R;Yusko E;Sanders C;Robins HS;Yong WH;Davidson TB;Li G;Liau LM;Prins RM
虽然免疫治疗策略正在成为癌症的辅助治疗，但监测治疗后免疫反应的敏感方法仍有待建立。我们使用了一种新的下一代测序（NGS）方法来确定脑肿瘤和外周血中肿瘤浸润淋巴细胞（TIL）含量的定量评估和T细胞受体（TCR）序列的重叠程度是否可以预测胶质母细胞瘤（GBM）患者接受自体肿瘤溶解物脉冲树突状细胞（DC）免疫治疗的免疫反应和总生存率。较高的估计TIL含量与增加的进展时间（TTP）和总生存期（OS）之间存在显著相关性。此外，我们能够评估治疗前后时间点肿瘤和外周血之间共享TCR序列的比例，并发现TCR重叠水平与生存结果相关。较高程度的重叠，或免疫治疗后重叠增加的发展，与改善的临床结果相关，并可能为成功的抗原特异性免疫反应提供见解。
While immunotherapeutic strategies are emerging as adjunctive treatments for cancer, sensitive methods of monitoring the immune response after treatment remain to be established. We used a novel next generation sequencing (NGS) approach to determine whether quantitative assessments of tumor infiltrating lymphocyte (TIL) content and the degree of overlap of T cell receptor (TCR) sequences in brain tumors and peripheral blood were predictors of immune response and overall survival in glioblastoma (GBM) patients treated with autologous tumor lysate-pulsed dendritic cell (DC) immunotherapy. A significant correlation was found between a higher estimated TIL content and increased time to progression (TTP) and overall survival (OS). In addition, we were able to assess the proportion of shared TCR sequences between tumor and peripheral blood at time points before and after therapy, and found the level of TCR overlap to correlate with survival outcomes. Higher degrees of overlap, or the development of an increased overlap following immunotherapy, correlated with improved clinical outcome, and may provide insights into the successful, antigen-specific immune response.