Journal
CANCER IMMUNOLOGY RESEARCH
Volume 8, Issue 1, Pages 146-154Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2326-6066.CIR-19-0398
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Funding
- National Natural Sciences Foundation Key Program [81630071]
- CAMS Innovation Fund for Medical Sciences (CIFMS) [2016-I2 M-3-008, 2017-I2 M-1-005]
- Aiyou Foundation [KY201701]
- Ministry of Education Innovation Team Development Project [IRT-17R10]
- CAMS Key Lab of Translational Research on Lung Cancer [2018PT31035]
- China National Natural Sciences Foundation [81871889]
- Beijing Natural Science Foundation [7172045]
- Beijing Novel Program Grants, cross-cooperation [Z181100006218130]
- Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences [2018RC320009]
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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 TCRb 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.
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