Fc gamma receptors and cancer

FcgammaRs are a family of heterogeneous molecules that play opposite roles in immune response and control the effector functions of IgG antibodies. In many cancers, IgG antibodies are produced that recognize cancer cells, form immune complexes and therefore, activate FcgammaR. The therapeutic efficacy of monoclonal IgG antibodies against hematopoietic and epithelial tumors also argue for an important role of IgG antibodies in anti-tumor defenses. Since the 1980s, a series of lines of evidence in experimental models and in humans strongly suggest that FcgammaR are involved in the therapeutic activity of monoclonal IgG antibodies by activating the cytotoxic activity of FcgammaR-positive cells such as NK cells, monocytes, macrophages and neutrophils and by increasing antigen presentation by dendritic cells. Since many cell types co-express activating and inhibitory FcgammaR, the FcgammaR-dependent effector functions of IgG anti-tumor antibodies are counterbalanced by the inhibitory FcgammaRIIB. In addition, some tumor cells express FcgammaR either constitutively, such as B cell lymphomas or ectopically, such as 40% of human metastatic melanoma. The tumor FcgammaR isoform is preferentially FcgammaRIIB, which is functional at least in human metastatic melanoma. This review summarizes these data and discusses how FcgammaRIIB expression may influence the anti-tumor immune reaction and how beneficial or deleterious this expression could be for the efficiency of therapeutics based on monoclonal anti-tumor antibodies.