Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Cancer Immunol Res. 2018 Feb;6(2):151-162. doi: 10.1158/2326-6066.CIR-17-0114. Epub 2017 Dec 20.
Despite a dramatic increase in T-cell receptor (TCR) sequencing, few approaches biologically parse the data in a fashion that both helps yield new information about immune responses and may guide immunotherapeutic interventions. To address this issue, we developed a method, ImmunoMap, that utilizes a sequence analysis approach inspired by phylogenetics to examine TCR repertoire relatedness. ImmunoMap analysis of the CD8 T-cell response to self-antigen (K-TRP2) or to a model foreign antigen (K-SIY) in naïve and tumor-bearing B6 mice showed differences in the T-cell repertoire of self- versus foreign antigen-specific responses, potentially reflecting immune pressure by the tumor, and also detected lymphoid organ-specific differences in TCR repertoires. When ImmunoMap was used to analyze clinical trial data of tumor-infiltrating lymphocytes from patients being treated with anti-PD-1, ImmunoMap, but not standard TCR sequence analyses, revealed a clinically predicative signature in pre- and posttherapy samples. .
尽管 T 细胞受体 (TCR) 测序有了显著的增加,但很少有方法能够以一种既能提供有关免疫反应的新信息,又能指导免疫治疗干预的方式对数据进行生物学解析。为了解决这个问题,我们开发了一种方法,ImmunoMap,它利用受系统发育启发的序列分析方法来检查 TCR 库的相关性。在 naive 和肿瘤荷瘤 B6 小鼠中,用 ImmunoMap 分析 CD8 T 细胞对自身抗原 (K-TRP2) 或模型外源抗原 (K-SIY) 的反应,显示出自反应和外源反应的 T 细胞库存在差异,这可能反映了肿瘤的免疫压力,并且还检测到了淋巴器官特异性 TCR 库的差异。当 ImmunoMap 用于分析接受抗 PD-1 治疗的患者肿瘤浸润淋巴细胞的临床试验数据时,ImmunoMap(但不是标准的 TCR 序列分析)揭示了治疗前和治疗后样本中的临床预测特征。