Concurrent Expression of CD47 and CD44 in Colorectal Cancer Promotes Malignancy

CD47 activates signal regulatory protein alpha expressed on macrophages and suppresses its phagocytic ability; therefore, CD47 is drawing attention as an immune checkpoint in the innate immune system. Expression of CD47 in cancer is thought to allow cancer cells to escape antitumor immunity of the innate immune system. In this study, expression of CD47 was examined by immunostaining in colorectal cancer (CRC) and compared with the expression of CD44, which is a marker for cancer stem cells. In 95 cases of stage II-IV CRC, CD47 and CD44 showed overexpression in 82 and 80 cases, respectively. Both expression levels correlated with distant metastasis. Moreover, the expression of CD47 and CD44 in each case showed a significant correlation. In stage III cases, disease-free survival of cases showing high expression of CD47 and CD44 was worse than that of the cases with low expression. Furthermore, 3 of the stage IV cases were administered nivolumab, a checkpoint inhibitor of the acquired immune system, and 2 patients showed recurrence thereafter. All recurrent tumors highly expressed CD47 and CD44 and showed the epithelial-mesenchymal transition (EMT) phenotype. Our results suggest that CD47 promotes the malignancy of CRC in association with EMT and enhances the stemness of cancer cells. Moreover, our study suggests that CD47 and CD44 are involved in imparting resistance to programmed cell death (PD)-1/PD-ligand 1 inhibitors.