Dendritic Cells in Shaping Anti-Tumor T Cell Response

Abstract

Among professional antigen-presenting cells, dendritic cells (DCs) orchestrate innate and adaptive immunity and play a pivotal role in anti-tumor immunity. DCs are a heterogeneous population with varying functions in the tumor microenvironment (TME). Tumor-associated DCs differentiate developmentally and functionally into three main subsets: conventional DCs (cDCs), plasmacytoid DCs (pDCs), and monocyte-derived DCs (MoDCs). There are two major subsets of cDCs in TME, cDC1 and cDC2. cDC1 is critical for cross-presenting tumor antigens to activate cytotoxic CD8+ T cells and is also required for priming earlier CD4+ T cells in certain solid tumors. cDC2 is vital for priming anti-tumor CD4+ T cells in multiple tumor models. pDC is a unique subset of DCs and produces type I IFN through TLR7 and TLR9. Studies have shown that pDCs are related to immunosuppression in the TME through the secretion of immunosuppressive cytokines and by promoting regulatory T cells. MoDCs differentiate separately from monocytes in response to inflammatory cues and infection. Also, MoDCs can cross-prime CD8+ T cells. In this review, we summarize the subsets and functions of DCs. We also discuss the role of different DC subsets in shaping T cell immunity in TME and targeting DCs for potential immunotherapeutic benefits against cancer.