Fig. 3

The utilization of immune checkpoint inhibitors such as the CTLA-4 antibody, the PD-1 antibodies, and the chimeric antigen receptor T cell (CAR-T) in tumor immunotherapy. A: The basic process of the CTLA-4 antibody and the PD-1 antibodies in tumor immunotherapy. Dendritic cells can activate T cells after digesting tumor cells in the tumor microenvironment. Then, T cells moves to tumor mass for tumor-cell killing. However, tumor cell can abrogate above process by CTLA-4 and PD-L1. For PD-L1, PD-L1 expressed on tumor cells can bind to PD-1 expressed on T cells. Then, this binding inhibited T cell activation. For CTLA-4, a naïve T cell-intrinsic inhibitor of T cell activation, can exert its function by trans-endocytosis of B7 (also called CD80/CD86) on dendritic cells. Then, naïve T cells lost the co-stimulatory signals from the interaction between CD28 on naïve T cells and B7 on dendritic cells. However, in this condition, naïve T cells receive signals by T cell receptor binding with its ligands, the complex of major histocompatibility complex antigen and peptide (MHC + P), which leads to T cell inactivation. As a result, tumor cells grow without the control of anti-tumor immunity. CTLA-4 antibody blocks the process of trans-endocytosis of B7 on dendritic cells and restore the tumor cell-killing ability of naïve T cells. Similarly, PD-1 antibodies restore the tumor-cell killing ability of T cells by preventing the binding between PD-L1 and PD-1. B: A schematic CAR-T therapy. The main processes of CAR-T therapy include obtaining T cells from blood, creating CAR-T cells, growing many CAR-T cells, and infusing CAR T cells into patient with cancer. At last, CAR-T cells can attack cancer cells