Reduced tumorigenicity and augmented leukocyte infiltration after monocyte chemotactic protein-3 (MCP-3) gene transfer: Perivascular accumulation of dendritic cells in peritumoral tissue and neutrophil recruitment within the tumor

Francesca Fioretti, Didier Fradelizi, Antonella Stoppacciaro, Simona Ramponi, Luigi Ruco, Adrian Minty, Silvano Sozzani, Cecilia Garlanda, Annunciata Vecchi, Alberto Mantovani

Research output: Contribution to journalArticle

Abstract

Monocyte chemotactic protein-3 (MCP-3) is a C-C chemokine that interacts with the CCR1, CCR2, and CCR3 receptors and has a spectrum of action encompassing T cells, NK cells, eosinophils, and dendritic cells (DC), in addition to mononuclear phagocytes. This broad spectrum of action prompted the present study aimed at assessing the antitumor activity of MCP-3 in a gene transfer approach and at providing information as to the actual in vivo leukocyte recruiting capacity of MCP-3. P815 mastocytoma cells transfected with the gene coding MCP-3 (P815/MCP-3) grew in syngeneic hosts and underwent rejection. Rejection was associated with profound alterations of leukocyte infiltration and resistance to subsequent challenge with P815 cells. Tumor- associated macrophages, already present in copious numbers, T cells, eosinophils, and neutrophils, increased in tumor tissues after gene transfer. DC, identified as DEC205+, high MHC class II+, CD11c+ cells, did not increase substantially in the tumor mass. However, in peritumoral tissues, DC accumulated in perivascular areas. P815/MCP.3-transfected tumor cells grew normally in nude mice. Increased accumulation of macrophages and polymorphonuclear neutrophils was evident also in nude mice. mAb against CD4, CD8, and IFN-γ, but not against IL-4, inhibited rejection of MCP-3- producing cells. An anti-polymorphonuclear mAb caused only a retardation of MCP-3-elicited tumor rejection. Thus, MCP-3 gene transfer elicits tumor rejection by activating type I T cell-dependent immunity. It is tempting to speculate that altered trafficking of APCs, which express receptors and respond to MCP-3, together with recruitment of activated T cells, underlies activation of specific immunity by MCP-3-transfected cells.

Original languageEnglish
Pages (from-to)342-346
Number of pages5
JournalJournal of Immunology
Volume161
Issue number1
Publication statusPublished - 1998

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Chemokine CCL7
Neutrophil Infiltration
Dendritic Cells
Leukocytes
Genes
Neoplasms
T-Lymphocytes
Eosinophils
Nude Mice
Immunity
CCR1 Receptors
CCR3 Receptors
Neutrophils
CCR2 Receptors
Macrophages
Mastocytoma
CC Chemokines
Phagocytes
Natural Killer Cells
Interleukin-4

ASJC Scopus subject areas

  • Immunology

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Reduced tumorigenicity and augmented leukocyte infiltration after monocyte chemotactic protein-3 (MCP-3) gene transfer : Perivascular accumulation of dendritic cells in peritumoral tissue and neutrophil recruitment within the tumor. / Fioretti, Francesca; Fradelizi, Didier; Stoppacciaro, Antonella; Ramponi, Simona; Ruco, Luigi; Minty, Adrian; Sozzani, Silvano; Garlanda, Cecilia; Vecchi, Annunciata; Mantovani, Alberto.

In: Journal of Immunology, Vol. 161, No. 1, 1998, p. 342-346.

Research output: Contribution to journalArticle

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abstract = "Monocyte chemotactic protein-3 (MCP-3) is a C-C chemokine that interacts with the CCR1, CCR2, and CCR3 receptors and has a spectrum of action encompassing T cells, NK cells, eosinophils, and dendritic cells (DC), in addition to mononuclear phagocytes. This broad spectrum of action prompted the present study aimed at assessing the antitumor activity of MCP-3 in a gene transfer approach and at providing information as to the actual in vivo leukocyte recruiting capacity of MCP-3. P815 mastocytoma cells transfected with the gene coding MCP-3 (P815/MCP-3) grew in syngeneic hosts and underwent rejection. Rejection was associated with profound alterations of leukocyte infiltration and resistance to subsequent challenge with P815 cells. Tumor- associated macrophages, already present in copious numbers, T cells, eosinophils, and neutrophils, increased in tumor tissues after gene transfer. DC, identified as DEC205+, high MHC class II+, CD11c+ cells, did not increase substantially in the tumor mass. However, in peritumoral tissues, DC accumulated in perivascular areas. P815/MCP.3-transfected tumor cells grew normally in nude mice. Increased accumulation of macrophages and polymorphonuclear neutrophils was evident also in nude mice. mAb against CD4, CD8, and IFN-γ, but not against IL-4, inhibited rejection of MCP-3- producing cells. An anti-polymorphonuclear mAb caused only a retardation of MCP-3-elicited tumor rejection. Thus, MCP-3 gene transfer elicits tumor rejection by activating type I T cell-dependent immunity. It is tempting to speculate that altered trafficking of APCs, which express receptors and respond to MCP-3, together with recruitment of activated T cells, underlies activation of specific immunity by MCP-3-transfected cells.",
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AU - Fioretti, Francesca

AU - Fradelizi, Didier

AU - Stoppacciaro, Antonella

AU - Ramponi, Simona

AU - Ruco, Luigi

AU - Minty, Adrian

AU - Sozzani, Silvano

AU - Garlanda, Cecilia

AU - Vecchi, Annunciata

AU - Mantovani, Alberto

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