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MIP-3 Transfection into a Rodent Tumor Cell Line Increases Intratumoral Dendritic Cell Infiltration but Enhances (Facilitates) Tumor Growth and Decreases Immunogenicity¹

Bernard Bonnotte^*,, Marka Crittenden^*, Nicolas Larmonier, Michael Gough^* and Richard G. Vile^2,*

^* Molecular Medicine Program and Department of Immunology, Mayo Clinic, Rochester, MN 55905; and Institut National de la Santé et de la Recherché Médicale Unité 517, Faculty of Medicine, Dijon, France

Dendritic cells are powerful APCs for activation of specific antitumor T lymphocytes. To present tumor Ags efficiently, they have first to migrate to the tumor site, engulf Ag, and then process them. To attract immature DCs to the tumor site, we transfected tumor cells with MIP-3 which is strongly chemotactic for DCs. Surprisingly, MIP-3-transfected tumor cells grew faster than the mock-transfected tumor cells. Histological analysis and tumor dissociation confirmed that the MIP-3-transfected tumors contain three to four times more DCs than mock-transfected tumors. FACS analysis of the intratumor DCs showed that they were predominantly immature. Functional analysis showed that the alloreactivity mediated by these infiltrating MIP-3-transfected tumor DCs is strongly reduced. In conclusion, MIP-3 is an efficient chemokine for attracting DCs in vivo, but the high density of DCs in the tumor site injection is not a sufficient condition to induce an immune response. Furthermore, this attraction of immature DCs may always have an adverse effect by inducing a tolerance to the tumor cells.

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