782-C Regulatory T-cell tumor infiltration is associated to better outcome in advanced NSCLC patients under ≥2nd line anti-PD1/L1 monotherapy in the PIONeeR project

BackgroundImmune checkpoint inhibitors (ICIs) are associated with long-term survival in ~20% of advanced NSCLC patients while biological mechanisms triggering resistance are not fully elucidated. The PIONeeR project (NCT03493581, ANR-17-RHUS-0007) aims to predict the response/resistance to PD1/L1 ICIs in advanced NSCLC patients through comprehensive agnostic multiparametric biomarkers assessment. The immune system is crucial for tumor evolution and is composed of different subsets of immune cells that can be activating (T-, B-lymphocytes, ...) or regulating such as regulatory T-cells (Treg).MethodsTumor was sampled at diagnosis from 101 advanced pretreated NSCLC patients, ECOG PS0/1, treated with standard PD1/L1 ICIs monotherapy. Complete database of ≥2nd line PIONeeR patients was released in July 2023. Overall Response Rate was assessed by RECIST 1.1. Multiplex IHC Brightplex® T-cells exhaustion quantifies cytotoxic (Tc) (CD3+CD8+) and helper (Th) (CD3+CD8-) T-lymphocytes in both tumor parenchyma and stroma. This quantification allows stratification into 4 tumor groups: Hot, Parenchyma Hot, Cold and Stroma Tumor Infiltrating Lymphocytes (TILs).1 2 Dual staining CD4 FOXP3 quantifies Treg density in parenchyma and stroma. Correlation analyses: spearman non-parametric test. Samples’ classification: unsupervised neural-network-based machine learning algorithm Self-Organizing Maps (SOM). Statistical significance of progression-free/overall survival (PFS/OS) differences: log-rank test. Response distribution differences: Fisher’s test.ResultsPatients were mainly male (65%), current/previous smoker (92%),