Fc receptors are required in passive and active immunity to melanoma

Effective tumor immunity requires recognition of tumor cells coupled with the activation of host effector responses, Fc receptor (FcR) gamma(-/-) mice, which lack the activating Fc gamma R types I and III, did not demonstrate protective timer immunity in models of passive and active immunization against a relevant tumor differentiation antigen, the brown locus protein gp75. In wild-type mice, passive immunization with mAb against gp75 or active immunization against gp75 prevented the development of lung metastases, This protective response was completely abolished in FcR gamma-deficient mice. Immune responses were intact in gamma(-/-) mice because IgG titers against gp75 develop normally in gamma(-/-) mice immunized with gp75, However, uncoupling of the Fc gamma R effector pathway from antibody recognition of tumor antigens resulted in a loss of protection against tumor challenge, These data demonstrate an unexpected and critical role for FcRs in mediating tumor cytotoxicity in vivo and suggest that enhancement of Fc gamma R-mediated antibody-dependent cellular cytotoxicity by inflammatory cells is a key step in the development of effective tumor immunotherapeutics.