Fig. 1

Immune checkpoint blockade. Professional antigen-presenting cells activate naive T cells through MHC-II complex/TCR and B7(CD80/86)/CD28 co-stimulatory binding. CTLA-4 inhibitors prevent competitive inhibitory binding of CTLA-4 with B7 ligands, which allows for more effective T cell activation. Activated effector T cells hone in on tumor cells and release IFNγ and other cytokines which boost the anti-tumor immune response. Tumor cells express PD-L1, which inhibits immune activity by binding to T cell PD-1 receptors, despite TCR recognition of target tumor antigens presented on tumor cell MHC-1 complex. Regulatory T cells (Tregs) also inhibit T cell activity and lead to an “exhausted” effector T cell phenotype. PD-1 inhibitors and PD-L1 inhibitors enhance the anti-tumor immune response by interrupting binding between tumor cell PD-L1 ligands and T cell PD-1 receptors. CTLA-4 cytotoxic T lymphocyte-associated antigen 4, MHC major histocompatibility complex, PD-1 programmed cell death protein 1, PD-L1 programmed death ligand 1, TCR T cell receptor