State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Minimally Invasive Tumor Therapies Center, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.
Oncoimmunology. 2021 Mar 17;10(1):1899609. doi: 10.1080/2162402X.2021.1899609.
An indicator for systemic evaluation of the adaptive immune status is lacking. Peripheral blood is important in antitumour immunity, and the T-cell receptor (TCR) repertoire diversity is key for effective immunity. This study aimed to investigate changes in the circulating T cell receptor β chain (TCRB) diversity during the first few (1 ~ 4) treatment cycles and its clinical value in patients with advanced lung cancer. TCRB-enriched sequencing data combined with transcriptomic RNA sequencing data of peripheral blood leukocytes were obtained from 72 patients with advanced lung cancer before and after targeted therapy or chemotherapy. Changes in the circulating TCRB diversity during treatment and the relationship of the baseline circulating TCRB diversity with prognosis and therapeutic effects were evaluated. We found that targeted therapy or chemotherapy did not significantly affect the T lymphocyte composition or circulating TCRB diversity (3.83 vs 3.74, T-test, = .16) in patients with advanced lung adenocarcinoma (LUAD) during the first few treatment cycles. The higher circulating TCRB diversity was linked to improved therapeutic effects (T-test, = .00083) in LUAD patients receiving targeted therapy. Higher baseline circulating TCRB diversity was associated with better prognosis. In addition, a five-factor prognostic risk score model was built for more accurate prognosis prediction for LUAD patients. The chemotherapeutic agents for advanced lung cancer do not significantly affect adaptive immune function over the first few treatment cycles. The circulating TCRB diversity reflects the adaptive immunological repertoire and might be a convenient indicator for evaluating the adaptive immune status and prognosis.
目前缺乏系统性评估适应性免疫状态的指标。外周血在抗肿瘤免疫中很重要,而 T 细胞受体 (TCR) 多样性是有效免疫的关键。本研究旨在探讨循环 T 细胞受体 β 链 (TCRB) 多样性在最初几个(1~4)治疗周期中的变化及其在晚期肺癌患者中的临床价值。从 72 名接受靶向治疗或化疗的晚期肺癌患者的外周血白细胞中获得了 TCRB 富集测序数据和转录组 RNA 测序数据。评估了治疗过程中循环 TCRB 多样性的变化以及基线循环 TCRB 多样性与预后和治疗效果的关系。我们发现,在最初几个治疗周期中,靶向治疗或化疗并未显著影响晚期肺腺癌(LUAD)患者的 T 淋巴细胞组成或循环 TCRB 多样性(3.83 与 3.74,T 检验, =.16)。较高的循环 TCRB 多样性与接受靶向治疗的 LUAD 患者的治疗效果改善相关(T 检验, =.00083)。较高的基线循环 TCRB 多样性与更好的预后相关。此外,还建立了一个包含 5 个预后因素的风险评分模型,用于更准确地预测 LUAD 患者的预后。晚期肺癌的化疗药物在前几个治疗周期中不会显著影响适应性免疫功能。循环 TCRB 多样性反映了适应性免疫库,可能是评估适应性免疫状态和预后的便捷指标。