Fig. 4

Immune checkpoints as modulators of the afferent and efferent arm of adaptive immunity. Cytotoxic T-lymphocyte protein 4 (CTLA-4) is an inhibitory receptor acting as a major negative regulator of T cell responses. As part of the afferent immune response CTLA-4 upregulation on antigen-activated T cells dampens the magnitude of T cell activation. At the efferent side, programmed death receptor 1 (PD-1) which is expressed on activated T cells blocks their effector functions upon binding to the ligands PD-L1 or PD-L2 on target cells. Tumor cells frequently use the expression of PD-L1 and PD-L2 to escape immune destruction