The TMB measured via circulating tumor DNA (ctDNA) in the blood is associated with response to ICBs and subsequent progression-free survival (PFS ref.
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. Patients with increased PD-1 + CD8 + TCR clonality after ICB treatment had longer PFS (7.3 months vs.
#TCR REPERTOIRE IMPORTANCE FOR MEDICAL TREATMENTS PLUS#
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). 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. Pre- and post-ICB peripheral blood samples were collected. Two independent patient cohorts (cohort A, n = 25 cohort B, n = 15) were used as discovery and validation sets, respectively. 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). T-cell receptor (TCR)–based biomarkers might predict patient response to immune checkpoint blockade (ICB) but need further exploration and validation for that use.
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