CD47 Expression in Classic Hodgkin Lymphoma and Its Association With Tumor Microenvironment

Cluster of differentiation 47 (CD47) has been reported to overexpress in various malignant tumors and is associated with inferior prognosis. However, the critical role of CD47 in classic Hodgkin lymphoma (CHL) and its association with immune checkpoints and tumor microenvironment (TME) remain unclear. Tumor tissues of CHL from Cancer Hospital, Chinese Academy of Medical Sciences and the public dataset from GSE17920 were analyzed. Immunohistochemistry was performed to detect the expression of CD47, programmed cell death protein 1 (PD-1), and PD ligand 1 (PD-L1) in CHL. Kaplan-Meier curves and Cox model were used for comparing the clinical outcomes of patients belonging to different subgroups. Bioinformatic analyses included differentially expressed genes (DEGs) screening, functional enrichment, and immune infiltration (CIBERSORT) were performed using GSE17920. In the study, CD47 expression was analyzed in both tumor cells (CD47tumor_score) and the TME (CD47micro_score) of CHL patients. High CD47tumor_score was associated with poorer progression-free survival (PFS) (p = 0.04). Meanwhile, high CD47micro_score was significantly correlated with worse PFS (p = 0.02). Univariate Cox regression identified high CD47micro_score as a significant predictor of inferior overall survival (OS; hazard ratio [HR] = 4.91, p = 0.03). Additionally, high CD47 expression correlated with increased PD-L1, and patients with concurrent high CD47 and positive PD-L1 of tumor cells had the shortest PFS, although this trend was not statistically significant. Importantly, a synergistic prognostic effect between CD47 and PD-L1 was that patients with high CD47 and/or PD-L1 of immune cells had significantly worse PFS than those with low expression of both markers. Analysis of public data (GSE17920) confirmed that high CD47 mRNA expression was associated with worse PFS (p = 0.02). Functional enrichment analyses revealed that high CD47 expression was linked to pathways involving chemokine signaling and immune cell migration, with increased infiltration of M1 macrophages, neutrophils, and eosinophils in the TME. CD47 might be involved in the disease progression and prognosis of CHL, it had a closely positive correlation with PD-L1. Targeting of CD47 and PD1/PDL1 might provide a promising strategy in CHL.