Toll-like receptor 2 ligand and interferon-γ suppress anti-tumor T cell responses by enhancing the immunosuppressive activity of monocytic myeloid-derived suppressor cells.

ABSTRACT: CD11b⁺Gr1⁺ myeloid-derived suppressor cells (MDSCs) suppress activation/proliferation of cytotoxic T cells, thereby hindering cancer immunotherapy. MDSCs are increased after adjuvant therapy with toll-like receptor (TLR) 2 ligands, such as Pam2CSK4, in tumor-bearing mice. However, it remains unknown if the activation of TLR2 in MDSCs affects their function and the therapeutic efficacy of TLR2 ligand. Here, we show that TLR2 signaling in CD11b⁺Ly6G^-Ly6C^high monocytic MDSCs (M-MDSCs), but not CD11b⁺Ly6G⁺Ly6C^low granulocytic MDSCs (G-MDSCs), enhances their immunosuppressive activity, thereby limiting anti-tumor T cell responses induced by TLR2-activated dendritic cells (DCs). iNOS induction was critical fo

SUBMITTER: Shime H 

PROVIDER: S-EPMC5739553 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature