RT Journal Article SR Electronic T1 TCR Repertoire Diversity of Peripheral PD-1+CD8+ T Cells Predicts Clinical Outcomes after Immunotherapy in Patients with Non–Small Cell Lung Cancer JF Cancer Immunology Research JO Cancer Immunol Res FD American Association for Cancer Research SP 146 OP 154 DO 10.1158/2326-6066.CIR-19-0398 VO 8 IS 1 A1 Han, Jiefei A1 Duan, Jianchun A1 Bai, Hua A1 Wang, Yuqi A1 Wan, Rui A1 Wang, Xin A1 Chen, Si A1 Tian, Yanhua A1 Wang, Di A1 Fei, Kailun A1 Yao, Zhuoran A1 Wang, Shuhang A1 Lu, Zhimin A1 Wang, Zhijie A1 Wang, Jie YR 2020 UL http://cancerimmunolres.aacrjournals.org/content/8/1/146.abstract AB 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.