Monocyte chemotactic cytokine gene transfer modulates macrophage infiltration, growth, and susceptibility to IL-2 therapy of a murine melanoma

B. Bottazzi, S. Walter, D. Govoni, F. Colotta, A. Mantovani

Research output: Contribution to journalArticle

Abstract

Tumor-derived chemotactic factors have been identified and suggested to play a role in the regulation of macrophage infiltration in neoplastic tissues. The present study was designed to assess the in vivo relevance of a tumor-derived chemotactic factor molecularly identified as monocyte chemotactic protein (MCP; alternative designations are JE and MCAF) by gene transfer in a murine melanoma. After gene transfer, MCP-producing melanoma clones showed a marked (twofold) increase in the percentage of tumor- associated macrophages compared with control clones and with the parent line: for instance, the percentage of tumor-associated macrophages was 20.9 ± 1.5, 29.4 ± 2.3, and 47.6 ± 2.5 for the parent line, the control V14 clone, and the MCP-producing L12 clone, respectively. MCP-producing cells were tumorigenic but exhibited a slower growth rate in vivo (e.g., doubling time of 2.9 and 6.6 days for the control V14 and the MCP-producing L12 clone, respectively) with a prolongation of survival time. The in vitro growth rate of melanoma clones was unaffected by MCP gene transfer. The same difference between MCP-producing and control cells, in terms of macrophage infiltration and growth rate, was detected after implantation in athymic mice. Whereas the in vivo growth rate of MCP-expressing tumors was slower, after i.m. inoculation of small cell numbers (10 2 cells) MCP-producing cells were slightly, but significantly, more tumorigenic. Local administration of IL-2 had modest, but definite, antitumor activity in this model; MCP-producing cells were less susceptible to local IL-2 immunotherapy. These results demonstrate that a tumor-derived chemotactic cytokine can indeed play a role in the regulation of mononuclear phagocyte recruitment in neoplastic tissues and emphasize how tumor-associated macrophages can exert a dual influence in tumor-host interactions.

Original languageEnglish
Pages (from-to)1280-1285
Number of pages6
JournalJournal of Immunology
Volume148
Issue number4
Publication statusPublished - 1992

ASJC Scopus subject areas

  • Immunology

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