Fig. 2

Effects of TGF-β on Antitumor Immunity. TGF-β is produced by multiple cell types within the TME. TGF-β can increase (black arrow) or decrease (red block) the proliferation and functional activity of immune effectors with tumor-promoting or tumor-suppressive outcomes. TGF-β enhances pro-inflammatory Th17 cells along with IL-6. TGF-β also blocks the IFN-γ-mediated induction of pro-inflammatory Th1 cells as well as the IL-4-dependent production of Th2 cells to decrease tumor suppression. TGF-β induces naïve T cell differentiation into Tregs and Treg expansion with IL-2. Tregs then reduce CD8⁺ T cell development and expansion to increase immune suppression. TGF-β also reduces the production of mast cells (to reduce superoxide and NO production), natural killer (NK) cells (reduced cytokine and IFN-γ production), B cells (reduced IgA secretion), polymorphonuclear cells (PMNs, reduced degranulation), M1 macrophages (reduced pro-inflammatory cytokines, e.g., IL-12) and reduced dendritic cells (DCs) leading to reduced antigen presentation and cytokine production. TGF-β promotes the differentiation and expansion of MDSCs as well as the production of M2 macrophages leading to increased anti-inflammatory cytokines IL-4 and IL-10