Immune Gene Signatures for Predicting Durable Clinical Benefit of Anti-PD-1 Immunotherapy in Patients with Non-small Cell Lung Cancer

Immune checkpoint blockade is promising for treating non-small-cell lung cancer (NSCLC). We used multipanel markers to predict the response to immune checkpoint inhibitors (ICIs) by characterizing gene expression signatures or individual genes in patients who showed durable clinical benefit to ICIs. Twenty-one patients with NSCLC treated with single-agent anti-programmed cell death protein (PD)-1 antibody were analyzed and their clinicopathological characteristics and response to ICIs were characterized. Nine (43%) showed a durable clinical benefit (DCB), while the remaining 12 (57%) patients showed non-durable benefit (NDB). The M1 and peripheral T cell signatures showed the best performance for discriminating DCB from NDB (sensitivity, specificity, accuracy = 0.89, 1.0, 0.95, respectively). Progression-free survival (PFS) was significantly longer in patients with high M1 signature or high peripheral T cell signature scores. CD137 and PSMB9 mRNA expression was higher in the DCB group than in the NDB group. Patients with high PSMB9 expression showed longer PFS. M1 signature, peripheral T cell signature and high mRNA expression level of CD137 and PSMB9 showed better predictive performance than known biomarkers, such as PD-L1 immunohistochemistry, tumor mutation burden, or tumor-infiltrating lymphocytes.