Hashemi S, Fransen MF, Niemeijer A, et al. - To determine if and how real-world clinicopathological variables, including tumor infiltrating lymphocytes (TILs) and programmed death-(ligand)1 (PD-L1), can impact anti-PD-1 efficacy, researchers analyzed advanced non-small cell lung cancer (NSCLC) cases managed with nivolumab or pembrolizumab between January 2015 and February 2019 in this monocenter retrospective analysis. Experts employed univariate and multivariate models to determine the effect of baseline clinical as well as pathological variables. There were 366 patients included in this study, 141 of whom were assessed for tumor and stromal TILs. Findings revealed that among patients with advanced NSCLC on anti-PD-1 therapy, progression free survival (PFS) and overall survival (OS) were most strongly predicted by stromal CD8 + TILs. PFS was predicted by albumin and and OS by albumin with lactate dehydrogenase. Stromal compartment was emphasized to have a pivotal role in the mechanisms of action of immune checkpoint inhibitors, and these data highlight the requirement for further investigations aiming to overcome this stromal firewall.