Factors Influencing the Differentiation of Human Monocytic Myeloid-Derived Suppressor Cells Into Inflammatory Macrophages.

ABSTRACT: Monocytic myeloid-derived suppressor cells (mMDSC) accumulate within tumors where they create an immunosuppressive milieu that inhibits the activity of cytotoxic T and NK cells thereby allowing cancers to evade immune elimination. The toll-like receptors 7/8 agonist R848 induces human mMDSC to mature into inflammatory macrophage (MAC_inflam). This work demonstrates that TNFα, IL-6, and IL-10 produced by maturing mMDSC are critical to the generation of MAC_inflam. Neutralizing any one of these cytokines significantly inhibits R848-dependent mMDSC differentiation. mMDSC cultured in pro-inflammatory cytokine IFNγ or the combination of TNFα plus IL-6 differentiate into MAC_inflam more efficiently than those treated with R848. These mMDSC-derived macrophages exert

SUBMITTER: Bayik D 

PROVIDER: S-EPMC5879147 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature