Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Cancer Immunol Res. 2016 May;4(5):412-418. doi: 10.1158/2326-6066.CIR-15-0240. Epub 2016 Mar 11.
Although 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 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 patients treated with autologous tumor lysate-pulsed dendritic cell immunotherapy. A statistically significant correlation was found between a higher estimated TIL content and increased time to progression and overall survival. 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, was correlated with improved clinical outcome, and may provide insights into the successful, antigen-specific immune response. Cancer Immunol Res; 4(5); 412-8. ©2016 AACR.
尽管免疫治疗策略正在成为癌症的辅助治疗方法,但仍需要建立敏感的方法来监测治疗后的免疫反应。我们使用一种新的下一代测序方法来确定脑肿瘤和外周血中肿瘤浸润淋巴细胞 (TIL) 含量的定量评估以及 T 细胞受体 (TCR) 序列的重叠程度是否可预测接受自体肿瘤裂解物脉冲树突细胞免疫治疗的胶质母细胞瘤患者的免疫反应和总生存。我们发现,较高的估计 TIL 含量与进展时间和总生存时间的增加呈统计学显著相关。此外,我们还能够在治疗前后的时间点评估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。较高的重叠程度,或免疫治疗后重叠程度的增加,与改善的临床结果相关,并且可能为成功的、抗原特异性的免疫反应提供见解。Cancer Immunol Res; 4(5); 412-8. ©2016 AACR.