Prognostic value of PD-L1 expression in combination with CD8+ TILs density in patients with surgically resected non-small cell lung cancer

Abstract

To investigate the prognostic value of PD-L1 expression combined with CD8⁺ TILs density in patients with resected NSCLC and correlations with clinicopathological features. We retrospectively enrolled 178 patients with resected NSCLC from 2011 to 2015. All surgical primary and 58 matched metastatic lymph node specimens were tested for PD-L1, CD8⁺ TILs, and oncogenic alterations. PD-L1⁺ was detected in 71 (39.9%) and CD8^high TILs in 74 (41.6%) cases. Smoking, SqCC, and EGFR^- were associated with both PD-L1⁺ and CD8^high TILs. Patients with CD8^high TILs had longer OS (P = 0.012). PD-L1^- was significantly associated with longer OS in patients with oncogenic alterations (P = 0.047). By multivariate analysis, CD8^high TILs (HR = 0.411; 95% CI, 0.177-0.954; P = 0.038), rather than PD-L1, was the independent predictive factor for OS. The longest and shortest OS were achieved in patients with PD-L1⁺ /CD8^high and PD-L1⁺ /CD8^low , respectively (P = 0.025). Inconsistent PD-L1 expression levels were observed in 23 of 58 (39.7%) patients with primary and matched metastatic lymph node specimens. Of them, CD8^high TILs was significantly associated with longer OS in patients with metastatic lymph nodes and/or consistent PD-L1 expression (P = 0.017 and 0.049, respectively). The combination of PD-L1 and CD8⁺ TILs density, instead of PD-L1 alone, suggested impressive prognostic values in NSCLC patients. Less than half of patients with resected NSCLC experienced inconsistent PD-L1 expression between primary and metastatic lesions. The level of PD-L1 expression in advanced NSCLC needs to be evaluated more comprehensively.

Keywords: CD8; non-small cell lung cancer; prognosis; programmed cell death ligand-1; tumor infiltrating lymphocytes.