Inflammation induces myeloid-derived suppressor cells that facilitate tumor progression

Stephanie K Bunt; Pratima Sinha; Virginia K Clements; Jeff Leips; Suzanne Ostrand-Rosenberg

doi:10.4049/jimmunol.176.1.284

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Inflammation induces myeloid-derived suppressor cells that facilitate tumor progression

Journal article

Peer reviewed

Inflammation induces myeloid-derived suppressor cells that facilitate tumor progression

Stephanie K Bunt, Pratima Sinha, Virginia K Clements, Jeff Leips and Suzanne Ostrand-Rosenberg

The Journal of immunology (1950), Vol.176(1), pp.284-290

01/01/2006

DOI: 10.4049/jimmunol.176.1.284

PMID: 16365420

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Abstract

Epidemiological and experimental observations support the hypothesis that chronic inflammation contributes to cancer development and progression; however, the mechanisms underlying the relationship between inflammation and cancer are poorly understood. To study these mechanisms, we have transfected the mouse 4T1 mammary carcinoma with the proinflammatory cytokine IL-1beta to produce a chronic inflammatory microenvironment at the tumor site. Mice with 4T1/IL-1beta tumors have a decreased survival time and elevated levels of immature splenic Gr1+CD11b+ myeloid-derived cells. These myeloid suppressor cells (MSC) are present in many patients with cancer and inhibit the activation of CD4+ and CD8+ T lymphocytes. 4T1/IL-1beta-induced MSC do not express the IL-1R, suggesting that the cytokine does not directly activate MSC. Neither T or B cells nor NKT cells are involved in the IL-1beta-induced increase of MSC because RAG2-/- mice and nude mice with 4T1/IL-1beta tumors also have elevated MSC levels. MSC levels remain elevated in mice inoculated with 4T1/IL-1beta even after the primary tumor is surgically removed, indicating that the IL-1beta effect is long lived. Collectively, these findings suggest that inflammation promotes malignancy via proinflammatory cytokines, such as IL-1beta, which enhance immune suppression through the induction of MSC, thereby counteracting immune surveillance and allowing the outgrowth and proliferation of malignant cells.

Animals

Cell Line, Tumor

Enzyme-Linked Immunosorbent Assay

Female

Flow Cytometry

Inflammation - immunology

Inflammation - physiopathology

Interleukin-1 - immunology

Interleukin-1 - metabolism

Killer Cells, Natural - immunology

Lymphocytes - immunology

Mammary Neoplasms, Experimental - immunology

Mice

Mice, Transgenic

Myeloid Cells - immunology

Transfection

Details

Title: Subtitle: Inflammation induces myeloid-derived suppressor cells that facilitate tumor progression
Creators: Stephanie K Bunt - University of Maryland, Baltimore County
Pratima Sinha - University of Maryland, Baltimore County
Virginia K Clements - University of Maryland, Baltimore County
Jeff Leips - University of Maryland, Baltimore County
Suzanne Ostrand-Rosenberg - University of Maryland, Baltimore County
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.176(1), pp.284-290
DOI: 10.4049/jimmunol.176.1.284
PMID: 16365420
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Grant note: CA52527 / NCI NIH HHS CA84232 / NCI NIH HHS
Language: English
Date published: 01/01/2006
Academic Unit: Family and Community Medicine
Record Identifier: 9984297345302771

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