Fig. 1.

Down-modulation of anti-tumour immune responses. Mechanisms for down-regulating anti-tumour immune responses can be categorized into tumour-intrinsic (left panel) and tumour-extrinsic (right panel). The first includes secretion of immunosuppressive cytokines or other soluble factors, alteration of immunogenicity and deletion or manipulation of tumour-associated antigen-specific effector cell function by the tumour cells or surrounding parenchyma. Tumour-intrinsic immunosuppressive mechanisms include secretion of immunosuppressive cytokines [interleukin (IL)-10 and transforming growth factor (TGF)-β], growth factors [vascular endothelial growth factor (VEGF)], or enzymes [indoleamine 2,3-dioxygenase (IDO)] and expression of inhibitory cell-surface molecules such as programmed cell death ligand (PD-L), Fas ligand (Fas-L), the co-inhibitory receptor B7 homologue 3 (B7-H3) and non-classical human leucocyte antigen (HLA) molecules (HLA-E/G). Tumour-intrinsic mechanisms promote a microenvironment that enhances regulatory T cell (T_reg) function. Extrinsic mechanisms involve a range of suppressive cells including suppressive T cells (inducible and natural T_regs and Tr1 T cells) and a heterogeneous population of myeloid-derived suppressor cells (MDSCs), alternatively activated M2-like tumour-associated macrophages (TAMs), immature antigen-presenting cells (APCs) and plasmacytoid dendritic cells (pDCs). The cells exert their effects via both interaction with infiltrating anti-tumour inflammatory cells and contribution to the suppressive tumour microenvironment.