TCR Repertoire Diversity of Peripheral PD-1 + CD8 + T Cells Predicts Clinical Outcomes after Immunotherapy in Patients with Non-Small Cell Lung Cancer

• Published in: Cancer immunology research 2020-01, Vol.8 (1), p.146-154
• Main Authors: Han, Jiefei, Duan, Jianchun, Bai, Hua, Wang, Yuqi, Wan, Rui, Wang, Xin, Chen, Si, Tian, Yanhua, Wang, Di, Fei, Kailun, Yao, Zhuoran, Wang, Shuhang, Lu, Zhimin, Wang, Zhijie, Wang, Jie
• Format: Article
• Language: English
• ISSN: 2326-6066; 2326-6074
• DOI: 10.1158/2326-6066.CIR-19-0398

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, = 25; cohort B, = 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; = 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; = 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.