Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Geneplus-Beijing Institute, Beijing, China.
Int J Cancer. 2019 Sep 1;145(5):1423-1431. doi: 10.1002/ijc.32145. Epub 2019 Jan 31.
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 β 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.
肺癌是对人类健康的最大威胁之一，最初是通过肿瘤反应性 T 细胞被免疫系统发现和攻击的。本研究旨在确定晚期肺癌患者外周血 T 细胞受体（TCR）谱的基本特征和临床意义。为了全面分析 TCR 谱，我们使用高通量测序技术鉴定了 64 名晚期肺癌患者和 31 名健康对照者外周血样本中 TCRβ 链互补决定区 3（CDR3）的高变区重排。我们发现，肺癌患者和健康对照者的 TCR 谱在 CDR3 克隆型、多样性、V/J 节段使用和序列方面存在显著差异。具体而言，基线多样性与多种临床特征相关，高多样性反映了更好的免疫状态。在抗癌治疗过程中对 TCR 谱进行动态检测对预后有帮助。治疗前后 TCR 谱的多样性增加和重叠率高均表明具有临床获益。将多样性和重叠率相结合，可将患者分为免疫改善或免疫恶化组，从而增强预后意义。总之，TCR 谱分析可作为晚期肺癌疾病进展和预后的有用指标，并可能用于指导未来的免疫治疗。
