TCR Repertoire Diversity of Peripheral PD-1+CD8+ T Cells Predicts Clinical Outcomes after Immunotherapy in Patients with Non–Small Cell Lung Cancer
| Autor: | Yanhua Tian, Yuqi Wang, Di Wang, Jiefei Han, Zhijie Wang, Zhimin Lu, Rui Wan, Kailun Fei, Jie Wang, Shuhang Wang, Si Chen, Zhuoran Yao, Xin Wang, Jianchun Duan, Hua Bai |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Oncology Cancer Research medicine.medical_specialty business.industry medicine.medical_treatment Immunology T-cell receptor Immunotherapy medicine.disease 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Antigen 030220 oncology & carcinogenesis Internal medicine Cohort medicine Cytotoxic T cell Lung cancer business Survival rate CD8 |
| Zdroj: | Cancer Immunology Research. 8:146-154 |
| ISSN: | 2326-6074 2326-6066 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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