Composite versus individual biomarkers for predicting clinical benefit to PD-1 blockade in NSCLC 111 3 ◀ Figure S3. Performance of PD-1T TILs and TIS as individual and as composite biomarker to predict disease control at 12 months (DC 12m) and association of CD8+IT-CD8 and CD8+TIS with DC 12m in NSCLC patients treated with PD-1 blockade. (A) Specificity correlating to a sensitivity and NPV of ≥90% for combinations with PD-1T TILs as predictive biomarker for DC 12m in the training cohort (n=27 or n=42). The grey dashed line indicates the prespecified specificity criterium of ≥50%. Different composite biomarkers were compared to the predictive performance of PD-1T TILs alone. P values were calculated by McNemar test. (B) Same plot as in A for combinations with TIS in the training cohort (n=27 or n=28). (C) Probability scores of CD8+IT-CD8 in pretreatment samples from patients with DC 12m (n=12) and progressive disease (PD) (n=43) in the training cohort (n=55). Dashed line indicates a cut-off of 0.122. Medians, interquartile ranges and minimum/maximum shown in boxplots, ***P<0.001 by Mann Whitney U-test. (D) Probability scores of CD8+TIS in pretreatment samples from patients with DC 12m (n=6) and PD (n=22) in the training cohort (n=28). Dashed line indicates a cut-off of 0.124. Medians, interquartile ranges and minimum/ maximum shown in boxplots, **P<0.01 by Mann Whitney U-test. (E) Probability scores of CD8+IT-CD8 in pretreatment samples from patients with DC 12m (n=16) and PD (n=61) in the validation cohort (n=77). Dashed line indicates a cut-off of 0.122. Medians, interquartile ranges and minimum/maximum shown in boxplots, *P=0.03 by Mann Whitney U-test. (F) Probability scores of CD8+TIS in pretreatment samples from patients with DC 12m (n=7) and PD (n=31) in the validation cohort (n=38). Dashed line indicates a cut-off of 0.124. Medians, interquartile ranges and minimum/maximum shown in boxplots, P=0.48 by Mann Whitney U-test. (G) PD-1T TILs per mm2 in pretreatment samples from patients with DC 12m (n=9) and PD (n=33) in the training cohort (n=42). Dashed line indicates a cut-off of 90 PD-1T TILs per mm2. Medians, interquartile ranges and minimum/maximum shown in boxplots, **P<0.01 by Mann Whitney U-test. (H) TIS scores in pretreatment samples from patients with DC 12m (n=6) and PD (n=22) in the training cohort (n=28). Dashed line indicates a cut-off score of 6.65. Medians, interquartile ranges and minimum/maximum shown in boxplots, *P=0.04 by Mann Whitney U-test.
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