Immune Suppression and Inflammation in the Progression of Breast Cancer
Abstract
Epidemiological and experimental observations support the hypothesis that chronic inflammation contributes to the development and progression of cancers; however the mechanisms underlying the relationship between inflammation and breast cancer are poorly understood. To study these mechanisms we have used an experimental mouse system in which 4T1 mammary carcinoma cells constitutively express the pro-inflammatory cytokine, IL-1 , resulting in an inflammatory microenvironment at the tumor site. Our results confirm the hypothesis that a pro-inflammatory microenvironment enhances tumor progression. More importantly, they suggest a novel mechanism by which inflammation facilitates tumor growth. We find that mice with IL-1 -producing tumors have in their spleens elevated levels of immature myeloid-derived cells with a Gr1+CD11b+ phenotype, which inhibit the activation of CD4+ and CD8+ T lymphocytes. Similar cells, termed myeloid suppressor cells, are frequently present in patients and experimental animals with tumors. These findings suggest that inflammation may promote malignancy by producing pro-inflammatory cytokines, such as IL-1 , that enhance systemic immune suppression through the induction of myeloid suppressor cells, thereby counteracting immune surveillance and allowing the outgrowth and proliferation of transformed cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2006
- Accession Number
- ADA462452
Entities
People
- Stephanie K. Bunt
Organizations
- University of Maryland, Baltimore