Brief Report|Articles in Press, 100498

High levels of CD47 expression in thymic epithelial tumors

Open AccessPublished:March 10, 2023DOI:
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      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 have not been tested in thymic epithelial tumors (TETs)—thymoma and thymic carcinoma. TETs are rare tumors which are difficult to treat, especially with PD-1/PD-L1 checkpoint inhibitors, due 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.


      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, USA) and scored for both intensity and H-score (intensity multiplied by the percentage of tumor involved). Intensity was defined as: 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 CD47low, while the rest were CD47high.


      Compared to normal thymic tissue, TETs were more frequently CD47 positive and had significantly higher levels of CD47 expression. CD47 was positive in 79.1% of TETs compared to 57.1% of normal thymus. The level of CD47 expression was 16-fold higher in TETs (mean H-score 75.0 vs 4.6, p = 0.003). Multivariate analysis adjusted for age, sex, stage, resection status, and performance status showed that CD47-high tumors were highly correlated with WHO histology (p = 0.028). The most frequent CD47high tumors, in contrast to CD47low tumors, were types A (28.6% vs 7.5%) and AB (57.1% vs 13.2%), and the least frequent were B1 (7.1% vs 24.5%), B2 (0% vs 35.8%), B3 (7.1% vs 11.3%) and C (0% vs 7.5%).


      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.