Crucial role of dendritic cells in the generation of anti-tumor T-cell responses and immunogenic tumor microenvironment to suppress tumor development

Abstract

Dendritic cells (DCs) are known as unique professional antigen (Ag)-presenting cells (APCs) to prime naïve T cells for the initiation of adaptive immunity. While DCs are believed to play a pivotal role in generating anti-tumor T-cell responses, the importance of DCs in the protection from the progression of tumors remains elusive. Here, we show how the constitutive deficiency of CD11c^hi DCs influences the progression of tumors with the use of binary transgenic mice with constitutive loss of CD11c^hi DCs. Constitutive loss of CD11c^hi DCs not only enhances the progression of tumors but also reduces the responses of Ag-specific T cells. Furthermore, the congenital deficiency of CD11c^hi DCs generates the immunosuppressive tumor microenvironment (TME) that correlates with the marked accumulation of myeloid-derived suppressor cells (MDSCs) and the prominent productions of immunosuppressive mediators. Thus, our findings suggest that CD11c^hi DCs are crucial for generating anti-tumor T-cell responses and immunogenic TME to suppress the development of tumors.

Keywords: anti-tumor T-cell responses; dendritic cells; immunosuppressive mediators; myeloid-derived suppressor cells; tumor development; tumor microenvironment.