Macrophages represent an important effector cell for Ab-mediated tumor therapy. Previous studies have documented that cytokines can influence Fc receptor (FcR) expression and function. In this study we examined the tumoricidal activities of the type I receptors for IgG (FcγRI) and the IgA FcR (FcαRI) on monocyte-derived macrophages (MDM) cultured in the presence of IFN-γ, M-CSF, or GM-CSF. Bispecific Abs were used to target a Her2/neu breast carcinoma cell line, SKBR-3, to FcαRI or FcγRI on MDM. Although FcαRI and FcγRI share a common signaling pathway contingent on association with the γ-chain (FcRγ subunit), a marked difference in their efficiency in mediating tumoricidal functions was seen in response to specific cytokines. M-CSF- and GM-CSF-treated MDM mediated efficient phagocytosis of SKBR-3 cells by FcαRI and FcγRI; however, IFN-γ-treated MDM phagocytosed tumor cells only with the FcγRI-directed bispecific Abs. Similarly, IFN-γ-cultured MDM lysed tumor cells more efficiently via FcγRI then by FcαRI as measured in Ab-dependent cellular cytotoxicity assays. Conversely, GM-CSF-treated MDM mediated more efficient lysis of tumor cells via FcαRI than FcγRI, while M- CSF-cultured MDM were relatively less efficient in mediating Ab-dependent cellular cytotoxicity through either receptor. With the exception of IFN-γ- mediated enhancement of FcγRI expression and FcγRI γ-chain complexes, the regulation of FcγRI- or FcαRI-mediated activity occurred without significant change in either receptor expression or total complexes with γ subunit. These data suggest that the efficiency of Ab-mediated tumor therapy, which depends on FcR effector cell functions, may be modified by the use of specific cytokines.
Keler, T., Wallace, P. K., Vitale, L. A., Russoniello, C., Sundarapandiyan, K., Graziano, R. F., & Deo, Y. M. (2000). Differential Effect of Cytokine Treatment on Fcα Receptor I- and Fcγ Receptor I-Mediated Tumor Cytotoxicity by Monocyte-Derived Macrophages. The Journal of Immunology, 164(11), 5746–5752. https://doi.org/10.4049/jimmunol.164.11.5746