Figure 5

A schematic diagram of the multi-organ process involved in immunosurveillance that becomes dysregulated in cancer. (A) Immature dendritic cells are recruited into peripheral tissues from the circulation. While in the peripheral tissues, biochemical cues within the tissue microenvironment educate immature DC. "Educated" mature DC downregulate tissue homing and upregulate chemokine receptors that promote DC emigration to the draining lymph node. Within the draining lymph node, mature DC present antigen, express costimulatory molecules, and secrete cytokines that influence T cell activation and polarization. The particular profile of cytokines secreted by mature DC is imprinted on immature DC while being educated in the peripheral tissues. (B) The presence of an epithelial tumor alters the profile of biochemical cues used to educate immature DC within the tissue microenvironment. In addition, the presence of metastatic tumor cells within the draining lymph nodes may interfere with the role that mature DC play in orchestrating an immune response. Therapeutic antibodies promote antibody-dependent cell-mediated cytotoxicity. Increased cell death by the carcinoma provides an additional source of tumor-associated antigens for immature DC to present in the draining lymph node.