Fig. 2

Dendritic cells (DCs) in antitumor immunity. DCs are recruited into the tumor bed by chemokines, such as CC chemokine ligands 4 (CCL4), CCL5, and XC-chemokine ligand 1 (XCL1). FMS-like tyrosine kinase 3 ligand (FLT3L) promotes the differentiation and survival of DCs. Immature DCs take up dying tumor cells that release damage-associated molecular patterns, migrate to the draining lymph nodes, and process and load cancer antigens onto human leukocyte antigen (HLA)-I and HLA-II for presentation to CD8⁺ and CD4⁺ T cells, respectively. Naive CD4⁺ T cells are primed first, which allows DCs to prime CD8⁺ T cells via CD40-CD40L signaling. Moreover, intratumoral DCs generate chemokines CXC-chemokine ligand 9 (CXCL9) and CXCL10 to recruit effector CD8⁺ T cells from draining lymph nodes. Tumors can change DC functions to achieve tumor immune escape. Vascular endothelial growth factor (VEGF) prevents DC differentiation and maturation. Activation of β-catenin signaling and expression of prostaglandin E₂ (PGE₂) prevent the recruitment of DCs to the tumor bed by blocking chemokine secretion, including CCL4, CCL5, and XCL1. PGE₂ prevents the recruitment and maturation of DCs. Tumor cells, CD4⁺ regulatory T cells (Treg), myeloid-derived suppressor cells (MDSCs), and M2 macrophages produce cytokines, including tumor growth factor-β (TGFβ), interleukin (IL)-6, IL-10, PGE₂, and VEGF, to prevent DC maturation. CCL4, CC-chemokine ligands 4; CXCL9, CXC-chemokine ligand 9; DAMP, damage-associated molecular pattern; DC, dendritic cell; FLT3L, FMS-like tyrosine kinase 3 ligand; HLA-I, class I human leukocyte antigen; IL-6, interleukin-6; MDSC, myeloid-derived suppressor cell; PGE₂, prostaglandin E₂; TGFβ, transforming growth factor-β; Treg cell, regulatory T cell; VEGF, vascular endothelial growth factor; XCL1, XC-chemokine ligand 1.