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.

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-gamma, 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.

• Authors: F Fioretti, D Fradelizi, A Stoppacciaro, S Ramponi, L Ruco, A Minty, S Sozzani, C Garlanda, A Vecchi, A Mantovani
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 161 Issue 1 Pg. 342-6 (Jul 01 1998) ISSN: 0022-1767 [Print] United States
• PMID: 9647242 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ccl7 protein, mouse
• Chemokine CCL7
• Cytokines
• Monocyte Chemoattractant Proteins

Topics

• Animals
• Cell Movement (genetics, immunology)
• Chemokine CCL7
• Cytokines
• Dendritic Cells (immunology, pathology)
• Gene Transfer Techniques
• Graft Rejection (genetics)
• Immunity, Innate
• Leukocytes (immunology)
• Male
• Mast-Cell Sarcoma (genetics, immunology, pathology)
• Mice
• Mice, Inbred DBA
• Mice, Nude
• Monocyte Chemoattractant Proteins (genetics)
• Neoplasm Transplantation
• Neutrophils (immunology, pathology)
• Transfection (immunology)