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J Immunol. 1998 Sep 1;161(5):2094-8.

Dendritic cells require maturation via CD40 to generate protective antitumor immunity.

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Department of Microbiology, Dartmouth Medical School, Lebanon, NH 03756, USA.


A critical role for CD40/CD154 interactions in the generation of protective cell-mediated tumor immunity has been demonstrated previously. Herein, 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. Furthermore, protective antitumor responses can be restored in CD40-deficient mice by the coadministration of CD40+/+ but not CD40-/- dendritic cells (DCs) with tumor Ag, suggesting that CD40 is critical for the maturation and function of DCs in vivo. Finally, we demonstrate that an IL-12-transduced but not a mock-transduced tumor vaccine induces systemic tumor immunity in anti-CD154-treated and CD154-deficient mice. These data suggest that impaired antitumor responses in the absence of CD40/CD154 interactions are the result of a lesion in APC function, namely IL-12 production, and that CD40 plays a critical role in the maturation of DCs in vivo.

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