Interferon-γ Enhances Monoclonal Antibody 17-1A-Dependent Neutrophil Cytotoxicity toward Colorectal Carcinoma Cell Line SW11-16

17-1A is a murine monoclonal antibody (MAb) specific for the tumor-associated antigen CO17-1A on colorectal carcinoma cells. One of the tumor cell destruction mechanisms induced by in vivo immunotherapy with MAb17-1A has been claimed to be antibody-dependent cellular cytotoxicity (ADCC) by monocytes and NK cells. In the present study we investigated whether human neutrophils (PMN) could be involved in colorectal carcinoma cell lysis and whether IFN-γ influences this function. We showed that neutrophils are capable of tumor lysis mediated by MAb17-1A, although to a lesser extent than are the mononuclear cells (PBMC). Neutrophil ADCC was, however, markedly increased in the presence of IFN-γ. Enhancement by IFN-γ was also observed for PBMC. ADCC by PMN required the binding of MAb17-1A to FcγRIII (CD16) since anti-FcγRIII MAbs efficiently blocked tumor cell lysis. In contrast, in the presence of IFN-γ the neutralization of FcγRIII did not affect MAb17-1A-mediated cytotoxicity, suggesting that receptors other than FcγRIII were involved in the process. PBMC cytotoxicity was also inhibited by anti-CD16 antibodies but IFN-γ did not overcome this effect. Finally, the scavenger enzymes superoxide dismutase and catalase did not block ADCC by PMN or PBMC, indicating that oxidants are not key factors in MAb17-1A-mediated lysis; however, in IFN-γ-activated PMN the oxygen-dependent mechanism was in part involved in tumor lysis.