Clinical implications of CD47 and programmed death-ligand 1 expression in predicting the therapeutic response of immune checkpoints in advanced nonsmall-cell lung cancer

PURPOSE: This study aimed to evaluate CD47 expression in nonsmall-cell lung cancer (NSCLC) and explore the predictive value of combined CD47 and programmed death-ligand 1 (PD-L1) status for immunotherapy outcomes. MATERIALS AND METHODS: Specimens from 59 patients with advanced NSCLC who were diagnosed or surgically resected and subsequently received immune checkpoint inhibitors (ICIs) were retrospectively collected for CD47 and PD-L1 detection by immunohistochemistry (IHC) and multiplex fluorescent IHC. A receiver operating characteristic (ROC) curve was constructed to determine the optimal CD47 cutoff value, and patients were categorized into four groups based on the IHC results: low CD47/negative-low PD-L1, high CD47/negative-low PD-L1, low CD47/high PD-L1, and high CD47/high PD-L1. In addition, the correlation between marker expression and clinical outcomes was analyzed. RESULTS: CD47 positivity was observed in 53 cases, 29 (54.7%) of which showed the coexpression of PD-L1/CD47. ROC analysis defined the threshold for high CD47 expression as >38.9% stained tumor cells. Multivariate analysis identified CD47 and PD-L1 as independent prognostic factors for immunotherapy efficacy (CD47: PFS P = 0.003, OS P = 0.001; PD-L1: PFS P = 0.424, OS P = 0.004). Subgroup analysis revealed that the low CD47/high PD-L1 group had the longest progression-free survival (PFS), not reaching the median, whereas the high CD47/negative-low PD-L1 group had the shortest PFS (median 131 days). Moreover, high CD47 expression was negatively correlated with PFS regardless of PD-L1 level. CONCLUSION: The combined assessment of CD47 and PD-L1 performed excellently in predicting responses to ICIs in advanced NSCLC, and this approach may serve as a potential predictive biomarker for immunotherapy.