Immune checkpoint therapy for pancreatic cancer

Figure 1 Flow diagram of article selection. ASCO: American Society of Clinical Oncology’s.

Figure 2 Check-point inhibition. A: Natural killer cell (NK cell) interacts with a PDA cell and gets activated through the binding of its activating receptor (AR) with PDA’s tumor associated antigen (TTA). Tolerance occurs when the programmed-death-receptor (PD-1) molecule on the NK cell interacts with its ligand, the programmed-death-ligand (PD-L1), on the PDA cell. Treatment with monoclonal antibody to bind these inhibitory proteins such as either α-PD-1 (Nivolumab, Pembrolizumab, Pidilizumab) or α-PD-L1 (Druvalumab, BMS-936559) prevents this interaction; B: CD8⁺ T cell interacts with a PDA cell and gets activated through the binding of its T cell receptor (TCR) with PDA’s major histocompatibility complex (MHC). Tolerance occurs when the PD-1 molecule on the NK cell interacts with PD-L1 on the PDA cell. Treatment with monoclonal antibody to bind these inhibitory proteins such as either α-PD-1 (Nivolumab, Pembrolizumab, Pidilizumab) or α-PD-L1 (Druvalumab, BMS-936559) prevents this interaction, resulting in suppression of T cell tumor attack; C: CD4⁺ helper T cell interacts with an antigen presenting cell (APC) through the binding of its TCR with APC’sMHC that present TAA. The co-stimulatory APC-signal-binding is induced by the CD28-B7-I/II interaction. The inhibitory checkpoint molecules: PD-L1, PD-1 and CTLA-4 are either presented before CD4⁺ activation or upregulated after activation and might result in inhibition and anergy of the helper T cell via PD-L1–PD-1, PD-L1–B7-1 and/or CTLA-4–B7-I/II interactions. Treatment with monoclonal antibody to bind these inhibitory proteins such as either α-PD-1 (Nivolumab, Pembrolizumab, Pidilizumab), α-PD-L1 (Druvalumab, BMS-936559) or α-CTLA-4 (Ipilimumab, Tremelimumab) can prevent this interaction, thus maintain antitumor activity.