Implication of gut microbiome in immunotherapy for colorectal cancer

Figure 1 Mechanism of action of both anti anti-cytotoxic TT-lymphocyte antigen-4 and anti-programmed cell death protein 1/programmed cell death 1 ligand 1 check point inhibitors. In the tumor microenvironment, antigen-presenting cells (APCs), such as dendritic cells processed specific tumor peptides (TAAs) and complexed them to major histocompatibility complex (MHC) molecules. Then, APC migrated to T cell-dependent areas of tumor presented TAA to naïve or quiescent T cells. Checkpoint inhibitor, such as anti-programmed cell death protein 1 (anti-PD-1)/anti-programmed cell death 1 ligand 1 (anti-PD-L1) and/oranti-cytotoxic TT-lymphocyte antigen-4 (anti-CTLA-4) on tumor cells, lead to re-activation of immune responses. The anti-PD-1 or anti-PD-L1 blocking by monoclonal antibodies (as nivolumab, pembrolizumab for PD-1 or atezolizumab for PD-L1) ipilimumab restore CD28 pro-activity signaling and restore effective anti-tumor T lymphocyte responses. The anti-CTLA-4 blocking by monoclonal antibodies as ipilimumab restore CD28 pro-activity signaling and result in effective anti-tumor T lymphocyte responses. The binding of PD-L1 to PD-1 and CTLA-4 to B7 keeps T cells from killing tumor cells in the body. Blocking the binding with an immune checkpoint inhibitor allows the T cells to kill tumor cells (upper panel).Chimeric antigen receptor (CAR) T cells are T cells that have been genetically engineered to produce an artificial T cell receptor for use in immunotherapy. CARs are receptor proteins that have been engineered to give T cells the new ability to target a specific protein (lower panel).