Myeloid-Derived Suppressor Cells (MDSC) polarize macrophages (MΦ) to a Type II tumor-promoting phenotype via MDSC-MΦ crosstalk. However, the role of inflammation in MDSC-MΦ crosstalk is not well defined. To determine the role of inflammation, we utilized wild type, IL-6-/-, and IL-10-/- mice bearing syngeneic 4T1 mammary carcinoma. MΦ and 4T1-induced MDSC express IL-6 and IL-10 receptors, suggesting that they have the potential to respond to both cytokines. To determine if IL-6 and IL-10 contribute to tumor progression by modulating MDSC-MΦ crosstalk, MDSC from 4T1-bearing wild type or IL-10-/- mice were cultured with MΦ from wild type or IL-6-/- mice. MDSC were anti-inflammatory and decreased MΦ production of IL-6. IL-6 is important in vivo since 4T1-bearing IL-6-/- mice have extended survival and delayed primary tumor growth vs. wild type mice. Anti-inflammatory effects are exacerbated by MΦ themselves, since their production of IL-6 increases MDSC production of IL-10. However, MΦ-produced IL-6 affects MDSC indirectly, as exogenous IL-6 does not increase MDSC IL-10 production. Although IL-10 is classically considered as an anti-inflammatory cytokine, it contributes to tumor progression because 4T1-bearing IL-10-/- mice have delayed primary tumor growth and extended survival vs. wild type mice. These data demonstrate that MDSC have anti-inflammatory effects and that MDSC-MΦ cross-talk contributes to the overall milieu of IL-10 and IL-6 within the tumor microenvironment.
- Copyright © 2013 by The American Association of Immunologists, Inc.