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Supplementary Table S3 from A Dysfunctional T-cell Gene Signature for Predicting Nonresponse to PD-1 Blockade in Non–small Cell Lung Cancer That Is Suitable for Routine Clinical Diagnostics

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posted on 2024-02-16, 09:40 authored by Karlijn Hummelink, Renaud Tissier, Linda J.W. Bosch, Oscar Krijgsman, Michel M. van den Heuvel, Willemijn S.M.E. Theelen, Diane Damotte, François Goldwasser, Karen Leroy, Egbert F. Smit, Gerrit A. Meijer, Daniela S. Thommen, Kim Monkhorst

Patient characteristics and treatment outcomes for training and validation cohorts. P-values were calculated by Mann-Whitney, Fisher exact or linear-by-linear association tests.

Funding

KWF Kankerbestrijding (DCS)

Dutch Ministry of Health, Welfare and Sport

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ARTICLE ABSTRACT

Because PD-1 blockade is only effective in a minority of patients with advanced-stage non–small cell lung cancer (NSCLC), biomarkers are needed to guide treatment decisions. Tumor infiltration by PD-1T tumor-infiltrating lymphocytes (TIL), a dysfunctional TIL pool with tumor-reactive capacity, can be detected by digital quantitative IHC and has been established as a novel predictive biomarker in NSCLC. To facilitate translation of this biomarker to the clinic, we aimed to develop a robust RNA signature reflecting a tumor's PD-1T TIL status. mRNA expression analysis using the NanoString nCounter platform was performed in baseline tumor samples from 41 patients with advanced-stage NSCLC treated with nivolumab that were selected on the basis of PD-1T TIL infiltration by IHC. Samples were included as a training cohort (n = 41) to develop a predictive gene signature. This signature was independently validated in a second cohort (n = 42). Primary outcome was disease control at 12 months (DC 12 m), and secondary outcome was progression-free and overall survival. Regularized regression analysis yielded a signature using 12 out of 56 differentially expressed genes between PD-1T IHC-high tumors from patients with DC 12 m and PD-1T IHC-low tumors from patients with progressive disease (PD). In the validation cohort, 6/6 (100%) patients with DC 12 m and 23/36 (64%) with PD were correctly classified with a negative predictive value (NPV) of 100% and a positive predictive value of 32%. The PD-1T mRNA signature showed a similar high sensitivity and high NPV as the digital IHC quantification of PD-1T TIL. This finding provides a straightforward approach allowing for easy implementation in a routine diagnostic clinical setting.