A dendritic cell vaccine targeting HER-2/neu alters antigen expression in ductal carcinoma in situ. Czerniecki et al. show that monocyte-derived dendritic cells activated with IFN-γ and the Toll-like receptor agonist bacterial lipopolysaccharide secrete at least two powerful bursts of IL-12; the first upon initial activation, and the second following CD40/CD40L interactions, such as delivered through DC contact with CD4^pos T cells. IL-12 can enhance CD8^pos CTL functional avidity and Th1 polarization, which potentially enhances complement-fixing antibody production by B cells. DCs pulsed with class I– and II–restricted HER-2/neu peptide epitopes were delivered intranodally to patients with early HER-2/neu–expressing breast carcinoma to test whether such a vaccination scheme could affect tumors. HER-2/neu expression on residual tumors within breast ducts dropped precipitously for several subjects as evidenced by immunohistochemical staining (brown) that compared prevaccine biopsy (left) and post vaccination surgical specimen (right). This study suggests that polarized DC1 vaccines can selectively target early tumors that express antigens such as HER-2/neu that are associated with greater aggressiveness and poorer prognosis. Future studies will determine whether such therapy can reduce risk of recurrence or invasive disease. For details, see the article by Czerniecki et al. on page 1842 of this issue.

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