Immune complex–mediated antigen presentation induces tumor immunity

Abstract

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 FcγRγ–/– DCs loaded with ovalbumin-containing immune complexes. Tumor protection was eliminated when immune complex–loaded DCs lacked β2 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.