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.