PMID: 9435247Jan 22, 1998Paper

Fc receptors are required in passive and active immunity to melanoma

Proceedings of the National Academy of Sciences of the United States of America
R ClynesJ V Ravetch

Abstract

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 tumor 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.

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