Crosstalk between Regulatory T Cells and Tumor-Associated Dendritic Cells Negates Anti-tumor Immunity in Pancreatic Cancer

Abstract

Regulatory T (Treg) cell infiltration constitutes a prominent feature of pancreatic ductal adenocarcinoma (PDA). However, the immunomodulatory function of Treg cells in PDA is poorly understood. Here, we demonstrate that Treg cell ablation is sufficient to evoke effective anti-tumor immune response in early and advanced pancreatic tumorigenesis in mice. This response is dependent on interferon-γ (IFN-γ)-producing cytotoxic CD8 + T cells. We show that Treg cells engage in extended interactions with tumor-associated CD11c + dendritic cells (DCs) and restrain their immunogenic function by suppressing the expression of costimulatory ligands necessary for CD8 + T cell activation. Consequently, tumor-associated CD8 + T cells fail to display effector activities when Treg cell ablation is combined with DC depletion. We propose that tumor-infiltrating Treg cells can promote immune tolerance by suppressing tumor-associated DC immunogenicity. The therapeutic manipulation of this axis might provide an effective approach for the targeting of PDA.