Fc receptors are required in passive and active immunity to melanoma

Fc receptors are required in passive and active immunity to melanoma

^*Laboratory of Molecular Genetics and Immunology, The Rockefeller University, 1230 York Avenue, and ^‡Immunology Program and Department of Medicine, Memorial Sloan–Kettering Cancer Center, 1275 York Avenue, New York, NY 10021

Edited by Henry Metzger, National Institutes of Health, Chevy Chase, MD, and approved December 9, 1997 (received for review October 9, 1997)

Abstract

Effective tumor immunity requires recognition of tumor cells coupled with the activation of host effector responses. Fc receptor (FcR) γ^−/− mice, which lack the activating FcγR 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 FcRγ-deficient mice. Immune responses were intact in γ^−/− mice because IgG titers against gp75 develop normally in γ^−/− mice immunized with gp75. However, uncoupling of the FcγR 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 FcγR-mediated antibody-dependent cellular cytotoxicity by inflammatory cells is a key step in the development of effective tumor immunotherapeutics.

Footnotes

↵ † To whom reprint requests should be addressed. e-mail: clynesr{at}rockvax.rockefeller.edu.
This paper was submitted directly (Track II) to the Proceedings Office.
Abbreviations: FcR, Fc receptor; NK, natural killer; ADCC, antibody-dependent cellular cytotoxicity; TNP, trinitrophenyl; wt, wild type.