Inflammation Induces Myeloid-Derived Suppressor Cells that Facilitate Tumor Progression
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Date
2006-01-01
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Citation of Original Publication
Stephanie K. Bunt, Pratima Sinha, Virginia K. Clements, Jeff Leips, Suzanne Ostrand-Rosenberg; Inflammation Induces Myeloid-Derived Suppressor Cells that Facilitate Tumor Progression. J Immunol 1 January 2006; 176 (1): 284–290. https://doi.org/10.4049/jimmunol.176.1.284
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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-1β to produce a chronic inflammatory microenvironment at the tumor site. Mice with 4T1/IL-1β 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-1β-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-1β-induced increase of MSC because RAG2⁻/⁻ mice and nude mice with 4T1/IL-1β tumors also have elevated MSC levels. MSC levels remain elevated in mice inoculated with 4T1/IL-1β even after the primary tumor is surgically removed, indicating that the IL-1β effect is long lived. Collectively, these findings suggest that inflammation promotes malignancy via proinflammatory cytokines, such as IL-1β, which enhance immune suppression through the induction of MSC, thereby counteracting immune surveillance and allowing the outgrowth and proliferation of malignant cells.