Il-12 Rapidly Alters the Functional Profile of Tumor-associated and Tumor-infiltrating Macrophages in Vitro and in Vivo.
From: Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY 40292, USA.
Journal of immunology (Baltimore, Md. : 1950)
- Publish Date: Feb 2007
- ISSN: 0022-1767
- Volume: 178
- Issue: 3
- Pages: 1357-62
- Medium: Print
- Language: English
- Citation (JAMA): Watkins Stephanie K, Egilmez Nejat K, Suttles Jill, et al. Il-12 Rapidly Alters the Functional Profile of Tumor-associated and Tumor-infiltrating Macrophages in Vitro and in Vivo.. J. Immunol. Feb 2007;178:1357-62
Abstract
Tumor-associated macrophages (TAMs) play a major role in promoting tumor growth and metastasis and in suppressing the antitumor immune response. Despite the immunosuppressive environment created by the tumor and enforced by tumor-associated macrophages, treatment of tumor-bearing mice with IL-12 induces tumor regression associated with appearance of activated NK cells and activated tumor-specific CTLs. We therefore tested the hypothesis that IL-12 treatment could alter the function of these tumor-associated suppressor macrophages. Analysis of tumor-infiltrating macrophages and distal TAMs revealed that IL-12, both in vivo and in vitro, induced a rapid (<90 min) reduction of tumor supportive macrophage activities (IL-10, MCP-1, migration inhibitory factor, and TGFbeta production) and a concomitant increase in proinflammatory and proimmunogenic activities (TNF-alpha, IL-15, and IL-18 production). Similar shifts in functional phenotype were induced by IL-12 in tumor-infiltrating macrophages isolated from the primary tumor mass and in TAMs isolated from lung containing metastases, spleen, and peritoneal cavity. Therefore, although TAMs display a strongly polarized immunosuppressive functional profile, they retain the ability to change their functional profile to proinflammatory activities given the appropriate stimulus. The ability of IL-12 to initiate this functional conversion may contribute to early amplification of the subsequent destructive antitumor immune response.
Mesh Headings (Keywords): Animals, Carcinoma, Lewis Lung, Cell Movement, Cytokines, Inflammation, Interleukin-12, Macrophages, Mice, Mice, Inbred C57BL, Neoplasms
Check for Full Text / PubMed Unique Identifier (PMID): 17237382
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