RT Journal Article
SR Electronic
T1 TCR Repertoire Diversity of Peripheral PD-1<sup>+</sup>CD8<sup>+</sup> 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.