Characteristics and prognostic significance of profiling the peripheral blood T-cell receptor repertoire in patients with advanced lung cancer
Characteristics and prognostic significance of profiling the peripheral blood T-cell receptor repertoire in patients with advanced lung cancer
复制标题
晚期肺癌患者外周血T细胞受体库特征及预后意义
DOI：
10.1002/ijc.32145
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发表时间：
2019-09-01
影响因子：
6.4
通讯作者：
Liu, Li
中科院分区：
文献类型：
--
作者：
Liu, Yang-Yang;Yang, Qi-Fan;Liu, Li
肺癌是对人类健康的最大威胁之一，并且最初通过肿瘤反应性T细胞被免疫系统检测和攻击。本研究旨在探讨晚期肺癌患者外周血T细胞受体（TCR）的基本特征及其临床意义。为了全面分析TCR谱系，使用高通量测序来鉴定64名晚期肺癌患者和31名健康对照外周血样本中TCR β链互补决定区3（CDR 3）的高变重排。我们发现，肺癌患者和健康对照组之间的TCR库在CDR 3克隆型、多样性、V/J片段使用和序列方面存在显著差异。具体而言，基线多样性与几个临床特征相关，高多样性反映了更好的免疫状态。动态检测TCR库在抗癌治疗过程中是有用的预后。治疗前和治疗后TCR库之间增加的多样性和高重叠率均表明临床益处。多样性和重叠率的组合用于将患者分类为免疫改善或免疫恶化组，并显示出增强的预后意义。总之，TCR库分析可作为晚期肺癌疾病发展和预后的有用指标，并可用于指导未来的免疫治疗。
Lung cancer is one of the greatest threats to human health, and is initially detected and attacked by the immune system through tumor-reactive T cells. The aim of this study was to determine the basic characteristics and clinical significance of the peripheral blood T-cell receptor (TCR) repertoire in patients with advanced lung cancer. To comprehensively profile the TCR repertoire, high-throughput sequencing was used to identify hypervariable rearrangements of complementarity determining region 3 (CDR3) of the TCR beta chain in peripheral blood samples from 64 advanced lung cancer patients and 31 healthy controls. We found that the TCR repertoire differed substantially between lung cancer patients and healthy controls in terms of CDR3 clonotype, diversity, V/J segment usage, and sequence. Specifically, baseline diversity correlated with several clinical characteristics, and high diversity reflected a better immune status. Dynamic detection of the TCR repertoire during anticancer treatment was useful for prognosis. Both increased diversity and high overlap rate between the pre- and post-treatment TCR repertoires indicated clinical benefit. Combination of the diversity and overlap rate was used to categorize patients into immune improved or immune worsened groups and demonstrated enhanced prognostic significance. In conclusion, TCR repertoire analysis served as a useful indicator of disease development and prognosis in advanced lung cancer and may be utilized to direct future immunotherapy.