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 TCRβ 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.

中文翻译：

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非小细胞肺癌患者免疫治疗后，外周PD-1 + CD8 + T细胞的TCR谱库多样性可预测临床结果。

基于T细胞受体（TCR）的生物标记物可能会预测患者对免疫检查点封锁（ICB）的反应，但需要对该方法进行进一步的探索和验证。我们对从PD-1 + CD8 + T细胞分离的TCRβ链的互补决定区3进行了测序，以研究其对预测抗程序性细胞死亡1（PD-1）/ PD-配体1（PD-L1）治疗的反应的价值在非小细胞肺癌（NSCLC）患者中。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。收集ICB前后的外周血样本。在队列A中，与低多样性患者相比，ICB治疗前PD-1 + CD8 + TCR多样性高的患者对ICB和无进展生存期（PFS）的反应更好[6.4个月vs. 2.5个月，HR，0.39；95％置信区间（CI）为0.17-0.94；P = 0.021]。结果在队列B中得到了验证。ICB之前的PD-1 + CD8 + TCR多样性达到了最佳尤登指数0.81（敏感性= 0.87，特异性= 0.94），以区分合并数据集中的ICB反应（队列A和队列B）。 。ICB治疗后PD-1 + CD8 + TCR克隆性增加的患者比克隆性降低的患者具有更长的PFS（7.3个月vs. 2.6个月，HR，0.26； 95％CI，0.08-0.86； P = 0.002）。因此，外周血PD-1 + CD8 + T细胞中的TCR多样性和克隆性可以作为患者对ICB反应和NSCLC生存结果的非侵入性预测指标。94），以区分合并后的数据集（同类群组A和同类群组B）中的ICB响应。ICB治疗后PD-1 + CD8 + TCR克隆性增加的患者比克隆性降低的患者具有更长的PFS（7.3个月vs. 2.6个月，HR，0.26； 95％CI，0.08-0.86； P = 0.002）。因此，外周血PD-1 + CD8 + T细胞中的TCR多样性和克隆性可以作为患者对ICB反应和NSCLC生存结果的非侵入性预测指标。94），以区分合并后的数据集（同类群组A和同类群组B）中的ICB响应。ICB治疗后PD-1 + CD8 + TCR克隆性增加的患者比克隆性降低的患者具有更长的PFS（7.3个月vs. 2.6个月，HR，0.26； 95％CI，0.08-0.86； P = 0.002）。因此，外周血PD-1 + CD8 + T细胞中的TCR多样性和克隆性可以作为患者对ICB反应和NSCLC生存结果的非侵入性预测指标。