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 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.
Clynes
R
R
Laboratory of Molecular Genetics and Immunology, Rockefeller University, New York, NY, USA. clynesr@rockvax.rockefeller.edu
Takechi
Y
Y
Moroi
Y
Y
Houghton
A
A
Ravetch
J V
JV
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology*; D007109:Immunity; D007116:Immunization, Passive; D008546:Melanoma, Experimental / Q000276:immunology*; D008562:Membrane Glycoproteins; D051379:Mice; D008810:Mice, Inbred C57BL; D010088:Oxidoreductases; D011506:Proteins / Q000276:immunology*; D011961:Receptors, Fc / Q000276:immunology*; D014611:Vaccination
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D008562:Membrane Glycoproteins; D011506:Proteins; D011961:Receptors, Fc; D010088:Oxidoreductases; C079621:Tyrp1 protein, mouse; C064056:tyrosinase-related protein-1