PD-L1 and CD47 co-expression predicts survival and enlightens future dual-targeting immunotherapy in non-small cell lung cancer.

ABSTRACT

BACKGROUD Recent studies have indicated that programmed cell death-ligand 1 (PD-L1) and cluster of differentiation 47 (CD47) play an essential role in tumor immune evasion and may serve as potential targets for combined immunotherapy. The aim of our study was to evaluate the PD-L1/CD47 expression status in lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD), and explore its survival impact and relevance with the immune microenvironment. METHODS: The specimens from 190 LUSC and 240 LUAD patients who underwent intent-to-treat surgeries were retrospectively collected for immunohistochemistry assays of PD-L1, CD47, cluster of differentiation 8 (CD8), and cluster of differentiation 68 (CD68). RESULTS: A total of 96 (22.3%) and 296 (68.8%) cases were positive for PD-L1 and CD47 expression, respectively, and 80 (18.6%) of them demonstrated the co-expression of PD-L1/CD47. The rate of PD-L1/CD47 co-expression was 23.7% in LUSC, significantly higher than the 14.6% in LUAD (p = 0.018). The median overall survival (OS) for all patients was 55.9 months (range 2.0-146.0 months). The univariate analysis showed that patients with positive CD47 expression (LUSC p = 0.003, LUAD p = 0.036) and PD-L1/CD47 co-expression (LUSC p = 0.023, LUAD p = 0.004) exhibited significantly worse prognosis. The multivariate analysis demonstrated that PD-L1/CD47 co-expression was an independent prognostic factor for OS (LUSC hazard ratio [HR] 1.922, 95% CI 1.245-2.969, p = 0.003; LUAD HR 1.549, 95% CI 1.015-2.364, p = 0.043). PD-L1/CD47 co-expression was associated with high CD8-positive T-lymphocyte density in LUSC (p = 0.004) and LUAD (p = 0.043), and with high CD68-positive macrophage density in LUSC (p = 0.026). CONCLUSIONS: PD-L1/CD47 co-expression was an independent prognostic factor for LUSC and LUAD patients and may serve as a potential predictive biomarker for combined dual-targeting immunotherapy.