A PD-1T signature as clinical applicable biomarker in NSCLC 143 4 Cut-off Sensitivity Specificity PPV NPV <0.35 vs ≥0.35 92% 93% 85% 96% <0.35 vs ≥0.35 100% 64% 32% 100% <50% vs ≥50% 50% 82% 33% 90% <1% vs ≥1% 50% 62% 19% 88% Next, we explored the predictive value of PDCD1 gene expression, encoding PD-1, and compared this to the PD-1T signature. Using all 58 pretreatment samples with available gene expression data from the first cohort for training, we observed that PDCD1 scores of the DC 12m group were slightly higher compared to the PD group (P=0.03), with an AUC of 0.71 (95% CI: 0.54-0.88) and a score of 0.20 as the optimal cut-off (Fig. S2A,B). In the validation cohort, signature scores did not significantly differ between the DC 12m group and the PD group (P=0.06) (Fig. S2C). The AUC was lower compared to the PD-1T signature (0.74; 95% CI: 0.50-0.99, P=0.36) (Fig. S2D), as well as the sensitivity (83%), NPV (93%) and specificity (36%) when using the predefined cut-off of 0.20 (Table S5). Patients with high (≥0.20) PDCD1 scores did not show significantly prolonged PFS and OS compared to those with low (<0.20) PDCD1 scores in the validation cohort (Fig. S2E,F). Taken together, these findings show that the PD-1T signature had a higher accuracy for predicting DC 12m and survival compared to PD-L1 TPS. The predictive performance of PDCD1 alone was lower as compared to the PD-1T signature, further highlighting that only the presence of a T cell subset with high expression of PD-1, which is reflected by the PD-1T signature, and not total PD-1 expression is predictive for response to PD-1 blockade.
RkJQdWJsaXNoZXIy MTk4NDMw