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.
J Immunol
; 161(1): 342-6, 1998 Jul 01.
Article
em En
| MEDLINE
| ID: mdl-9647242
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
/
Movimento Celular
/
Citocinas
/
Sarcoma de Mastócitos
/
Técnicas de Transferência de Genes
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Proteínas Quimioatraentes de Monócitos
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Leucócitos
/
Neutrófilos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Immunol
Ano de publicação:
1998
Tipo de documento:
Article