Immune complex-mediated antigen presentation induces tumor immunity

J Clin Invest. 2002 Jul;110(1):71-9. doi: 10.1172/JCI15640.


Antigen uptake receptors on dendritic cells (DCs) provide efficient entry for the initiation of antigen-specific adaptive immunity. Here we show that targeting of antigen to Fc receptors on DCs accomplishes combined activation of Th1 CD4 and CD8 effector responses in vivo, namely delayed-type hypersensitivity and tumor immunity. Tumor immunity specific for ovalbumin-expressing tumors was provided by immunization with wild-type but not FcgammaRgamma(-/-) DCs loaded with ovalbumin-containing immune complexes. Tumor protection was eliminated when immune complex-loaded DCs lacked beta(2) microglobulin, TAP, or MHC class II, demonstrating that Fc receptor-targeted antigenic uptake led to both MHC class I- and class II-restricted responses, which together are required for effector tumor immunity. Thus the cross-presentation pathway accessed by antigens acquired endocytically through Fc receptors links humoral and cellular immunity. These data suggest that administration of antitumor antibodies may enhance tumor-specific T cell responses in vivo and provide the rationale for Fc receptor targeting in vaccine development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neoplasm / biosynthesis
  • Antigen Presentation*
  • Antigen-Antibody Complex / metabolism*
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines / immunology
  • Dendritic Cells / immunology
  • Histocompatibility Antigens Class I / metabolism
  • Histocompatibility Antigens Class II / metabolism
  • Immunization, Passive
  • Melanoma, Experimental / immunology*
  • Melanoma, Experimental / therapy
  • Mice
  • Mice, Congenic
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Ovalbumin / immunology
  • Receptors, IgE / genetics
  • Receptors, IgE / metabolism
  • Tumor Cells, Cultured


  • Antibodies, Neoplasm
  • Antigen-Antibody Complex
  • Cancer Vaccines
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • Receptors, IgE
  • Ovalbumin