TCR Repertoire Diversity of Peripheral PD-1+CD8+ T Cells Predicts Clinical Outcomes after Immunotherapy in Patients with Non-Small Cell Lung Cancer
TCR Repertoire Diversity of Peripheral PD-1+CD8+ T Cells Predicts Clinical Outcomes after Immunotherapy in Patients with Non-Small Cell Lung Cancer
复制标题
外周 PD-1( )CD8( ) T 细胞的 TCR 库多样性可预测非小细胞肺癌患者免疫治疗后的临床结果
DOI：
10.1158/2326-6066.cir-19-0398
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发表时间：
2020-01-01
影响因子：
10.1
通讯作者：
Wang, Jie
中科院分区：
文献类型：
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作者：
Han, Jiefei;Duan, Jianchun;Wang, Jie
基于T细胞受体（TCR）的生物标志物可能预测患者对免疫检查点阻断（ICB）的反应，但需要进一步探索和验证。我们对从PD-1（+）CD 8（+）T细胞中分离的TCR b链的互补决定区3进行测序，以研究其预测非小细胞肺癌（NSCLC）患者对抗程序性细胞死亡1（PD-1）/PD-配体1（PD-L1）治疗的反应的价值。两个独立的患者队列（队列A，n = 25;队列B，n = 15）分别用作发现和验证集。采集ICB前后外周血样本。在队列A中，ICB治疗前PD-1（+）CD 8（+）TCR多样性高的患者对ICB的应答和无进展生存期（PFS）优于多样性低的患者[6.4个月vs. 2.5个月，HR，0.39; 95%置信区间（CI），0.17-0.94; P = 0.021]。在队列B中验证了结果。IC B治疗前PD-1（+）CD 8（+）TCR多样性在合并数据集（队列A加队列B）中达到区分IC B应答的最佳约登指数0.81（灵敏度= 0.87，特异性= 0.94）。ICB治疗后PD-1（+）CD 8（+）TCR克隆性增加的患者的PFS（7.3个月vs. 2.6个月，HR，0.26; 95% CI，0.08-0.86; P = 0.002）长于克隆性降低的患者。因此，外周血PD-1（+）CD 8（+）T细胞的TCR多样性和克隆性可作为NSCLC患者对ICB反应和生存结局的非侵入性预测因子。
T-cell receptor (TCR)-based biomarkers might predict patient response to immune checkpoint blockade (ICB) but need further exploration and validation for that use. We sequenced complementarity-determining region 3 of TCRb chains isolated from PD-1(+) CD8(+) T cells to investigate its value for predicting the response to anti-programmed cell death 1 (PD-1)/PD-ligand 1 (PD-L1) therapy in patients with non-small cell lung cancer (NSCLC). Two independent patient cohorts (cohort A, n = 25; cohort B, n = 15) were used as discovery and validation sets, respectively. Pre- and post-ICB peripheral blood samples were collected. In cohort A, patients with high PD-1(+) CD8(+) TCR diversity before ICB treatment showed better response to ICB and progression-free survival (PFS) compared with patients with low diversity [6.4 months vs. 2.5 months, HR, 0.39; 95% confidence interval (CI), 0.17-0.94; P = 0.021]. The results were validated in cohort B. Pre-ICB PD-1(+) CD8(+) TCR diversity achieved an optimal Youden's index of 0.81 (sensitivity = 0.87 and specificity = 0.94) for differentiating the ICB response in the merged dataset (cohort A plus cohort B). Patients with increased PD-1(+) CD8(+) TCR clonality after ICB treatment had longer PFS (7.3 months vs. 2.6 months, HR, 0.26; 95% CI, 0.08-0.86; P = 0.002) than those with decreased clonality. Thus, TCR diversity and clonality in peripheral blood PD-1(+) CD8(+) T cells may serve as noninvasive predictors of patient response to ICB and survival outcomes in NSCLC.