Abstract
INTRODUCTION: CD47 is a tumor antigen that inhibits phagocytosis leading to immune evasion. Anti-CD47 therapy is a promising new immunotherapy across numerous tumor types, but it has not been tested in thymic epithelial tumors (TETs): thymomas and thymic carcinomas. TETs are rare tumors that are difficult to treat, especially with programmed cell death protein 1/programmed death-ligand 1 checkpoint inhibitors, owing to the excessive rates of immune-related adverse events. This study investigated the levels of CD47 expression in TETs to explore the possibility of anti-CD47 therapy. METHODS: A total of 67 thymic tumors (63 thymomas and 4 thymic carcinomas) and 14 benign thymus controls and their clinical data were included. Samples were stained for CD47 expression (rabbit monoclonal antibody SP279, Abcam, Waltham, MA) and scored for both intensity and H-score (intensity multiplied by the percentage of tumor involved). Intensity was defined as follows: 0 = none, 1 = weak, 2 = moderate, and 3 = strong. H-scores ranged from 0 to 300. Samples with an intensity score below 2 or an H-score below 150 were considered CD47(low), whereas the rest were CD47(high). RESULTS: Compared with normal thymic tissues, TETs were more frequently CD47 positive and had significantly higher levels of CD47 expression. CD47 was positive in 79.1% of TETs compared with 57.1% of normal thymus. The level of CD47 expression was 16-fold higher in TETs (mean H-score 75.0 versus 4.6, p = 0.003). Multivariate analysis adjusted for age, sex, stage, resection status, and performance status revealed that CD47-high tumors were highly correlated with WHO histology type (p = 0.028). The most frequent CD47(high) tumors, in contrast to CD47(low) tumors, were types A (28.6% versus 7.5%) and AB (57.1% versus 13.2%), and the least frequent were B1 (7.1% versus 24.5%), B2 (0% versus 35.8%), B3 (7.1% versus 11.3%), and C (0% versus 7.5%). CONCLUSIONS: In contrast to normal thymus, TETs had significantly higher levels of CD47 expression. Tumor samples with high CD47 expression were mostly WHO types A and AB. This is the first study to explore CD47 expression in thymic cancers and lends support for ongoing investigation of anti-CD47 macrophage checkpoint inhibitor therapy in these tumors.