MIP-3alpha transfection into a rodent tumor cell line increases intratumoral dendritic cell infiltration but enhances (facilitates) tumor growth and decreases immunogenicity.
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-3alpha which is strongly chemotactic for DCs. Surprisingly, MIP-3alpha-transfected tumor cells grew faster than the mock-transfected tumor cells. Histological analysis and tumor dissociation confirmed that the MIP-3alpha-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-3alpha-transfected tumor DCs is strongly reduced. In conclusion, MIP-3alpha 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.
Molecular Medicine Program, Mayo Clinic, Rochester, MN 55905, USA.
Bernard
B
Bonnotte
Marka
M
Crittenden
Nicolas
N
Larmonier
Michael
M
Gough
Richard G
RG
Vile
D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D054418:Chemokine CCL20; D019742:Chemokines, CC / Q000502:physiology*; D003713:Dendritic Cells / Q000502:physiology*; D007959:Lymphocyte Culture Test, Mixed; D019402:Macrophage Inflammatory Proteins / Q000502:physiology*; D051379:Mice; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology; D051381:Rats; D014162:Transfection
C486997:Ccl20 protein, rat; D054418:Chemokine CCL20; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins