OBJECTIVE Integrin-associated protein (CD47) binds specifically to the inhibitory receptor signal-regulatory protein. This study was designed to evaluate the role of CD47 in natural killer (NK) cell-mediated cytotoxicity against cancer cells.

METHODS Head-and-neck squamous cell carcinoma (HNSCC) cell lines were analyzed for the expression of CD47 and susceptibility to NK cell-mediated killing. Cytolytic activity was assessed by (51)Cr-specific release assays and by measuring cytokine production.

RESULTS HNSCC cell lines that had high CD47 expression showed lower levels of NK cytotoxicity than those with low CD47 expression. After pre-treating cells with neutralizing major histocompatibility complex (MHC) class I or anti-CD47 antibodies, NK cell-mediated cytotoxicity against HNSCC cell lines increased. In addition, when CD47 cDNA was transfected into Caco-2 cells, NK cell-mediated cytotoxicity decreased.

CONCLUSION These findings suggest that CD47 may play an inhibitory role in NK cell-mediated cytotoxicity against cancer cells, implying a possible mechanism of immune escape in human cancer.