MIP-3α transfection into a rodent tumor cell line increases intratumoral dendritic cell infiltration but enhances (facilitates) tumor growth and decreases immunogenicity

Bernard Bonnotte, Marka Crittenden, Nicolas Larmonier, Michael Gough, Richard G. Vile

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39 Citations (Scopus)

Abstract

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-3α which is strongly chemotactic for DCs. Surprisingly, MIP-3α-transfected tumor cells grew faster than the mock-transfected tumor cells. Histological analysis and tumor dissociation confirmed that the MIP-3α 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-3α-transfected tumor DCs is strongly reduced. In conclusion, MIP-3α 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.

Original languageEnglish (US)
Pages (from-to)4929-4935
Number of pages7
JournalJournal of Immunology
Volume173
Issue number8
StatePublished - Oct 15 2004
Externally publishedYes

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Tumor Cell Line
Dendritic Cells
Transfection
Rodentia
Growth
Neoplasms
Chemokines
T-Lymphocytes
Injections

ASJC Scopus subject areas

  • Immunology

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MIP-3α transfection into a rodent tumor cell line increases intratumoral dendritic cell infiltration but enhances (facilitates) tumor growth and decreases immunogenicity. / Bonnotte, Bernard; Crittenden, Marka; Larmonier, Nicolas; Gough, Michael; Vile, Richard G.

In: Journal of Immunology, Vol. 173, No. 8, 15.10.2004, p. 4929-4935.

Research output: Contribution to journalArticle

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AU - Crittenden, Marka

AU - Larmonier, Nicolas

AU - Gough, Michael

AU - Vile, Richard G.

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N2 - 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-3α which is strongly chemotactic for DCs. Surprisingly, MIP-3α-transfected tumor cells grew faster than the mock-transfected tumor cells. Histological analysis and tumor dissociation confirmed that the MIP-3α 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-3α-transfected tumor DCs is strongly reduced. In conclusion, MIP-3α 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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