CUTTING EDGE - DENDRITIC CELLS REQUIRE MATURATION VIA CD40 TO GENERATE PROTECTIVE ANTITUMOR IMMUNITY

A critical role for CD40/CD154 interactions in the generation of prote ctive cell-mediated tumor immunity has been demonstrated previously. H erein, we show that the failure to generate systemic tumor immunity in the absence of CD40/CD154 interactions correlates with an inhibition of Th1-type cytokine production following tumor vaccination. Furthermo re, protective antitumor responses can be restored in CD40-deficient m ice by the coadministration of CD40(+/+) but not CD40(-/-) dendritic c ells (DCs) with tumor Ag, suggesting that CD40 is critical for the mat uration and function of DCs in vivo. Finally, we demonstrate that an I L-12-transduced but not a mock-transduced tumor vaccine induces system ic tumor immunity in anti-CD154-treated and CD154-deficient mice, Thes e data suggest that impaired antitumor responses in the absence of CD4 0/CD154 interactions are the result of a lesion in APC function, namel y IL-12 production, and that CD40 plays a critical role in the maturat ion of DCs in vivo.