American Association for Cancer Research
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Supplementary Figure from PD-1T TILs as a Predictive Biomarker for Clinical Benefit to PD-1 Blockade in Patients with Advanced NSCLC

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posted on 2023-04-01, 00:02 authored by Karlijn Hummelink, Vincent van der Noort, Mirte Muller, Robert D. Schouten, Ferry Lalezari, Dennis Peters, Willemijn S.M.E. Theelen, Viktor H. Koelzer, Kirsten D. Mertz, Alfred Zippelius, Michel M. van den Heuvel, Annegien Broeks, John B.A.G. Haanen, Ton N. Schumacher, Gerrit A. Meijer, Egbert F. Smit, Kim Monkhorst, Daniela S. Thommen
Supplementary Figure from PD-1T TILs as a Predictive Biomarker for Clinical Benefit to PD-1 Blockade in Patients with Advanced NSCLC


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Durable clinical benefit to PD-1 blockade in non–small cell lung cancer (NSCLC) is currently limited to a small fraction of patients, underlining the need for predictive biomarkers. We recently identified a tumor-reactive tumor-infiltrating T lymphocyte (TIL) pool, termed PD-1T TILs, with predictive potential in NSCLC. Here, we examined PD-1T TILs as biomarker in NSCLC. PD-1T TILs were digitally quantified in 120 baseline samples from advanced NSCLC patients treated with PD-1 blockade. Primary outcome was disease control (DC) at 6 months. Secondary outcomes were DC at 12 months and survival. Exploratory analyses addressed the impact of lesion-specific responses, tissue sample properties, and combination with other biomarkers on the predictive value of PD-1T TILs. PD-1T TILs as a biomarker reached 77% sensitivity and 67% specificity at 6 months, and 93% and 65% at 12 months, respectively. Particularly, a patient group without clinical benefit was reliably identified, indicated by a high negative predictive value (NPV) (88% at 6 months, 98% at 12 months). High PD-1T TILs related to significantly longer progression-free (HR 0.39, 95% CI, 0.24–0.63, P < 0.0001) and overall survival (HR 0.46, 95% CI, 0.28–0.76, P < 0.01). Predictive performance was increased when lesion-specific responses and samples obtained immediately before treatment were assessed. Notably, the predictive performance of PD-1T TILs was superior to PD-L1 and tertiary lymphoid structures in the same cohort. This study established PD-1T TILs as predictive biomarker for clinical benefit to PD-1 blockade in patients with advanced NSCLC. Most importantly, the high NPV demonstrates an accurate identification of a patient group without benefit.See related commentary by Anagnostou and Luke, p. 4835

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