Fc receptors are required in passive and active immunity to melanoma

Proc Natl Acad Sci U S A. 1998 Jan 20;95(2):652-6. doi: 10.1073/pnas.95.2.652.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antigens, Neoplasm / immunology*
  • Immunity*
  • Immunization, Passive
  • Melanoma, Experimental / immunology*
  • Membrane Glycoproteins*
  • Mice
  • Mice, Inbred C57BL
  • Oxidoreductases*
  • Proteins / immunology*
  • Receptors, Fc / immunology*
  • Vaccination

Substances

  • Antibodies, Monoclonal
  • Antigens, Neoplasm
  • Membrane Glycoproteins
  • Proteins
  • Receptors, Fc
  • Oxidoreductases
  • Tyrp1 protein, mouse
  • tyrosinase-related protein-1