Strategies and Advancements in Harnessing the Immune System for Gastric Cancer Immunotherapy

Figure 2

Immune checkpoint targeting. T cells recognize MHC-antigen complex through the primed T cell receptor (TCR) and CTLA-4 competes with CD28 to bind to costimulatory molecule B7 on antigen-presenting cells (APCs). This causes the initiation of an inhibitory signal that leads to suppression of T cell activation resulting in the failure to induce an effective antitumor responses [19]. Anti-CTLA-4 antibodies block this inhibitory signal and thus enhance the antitumor immunity through T cell proliferation and tumor-specific cytotoxicity. During the effector phase of T cell response, programmed death-1 (PD-1) inhibitory receptor is expressed by T cells after antigen exposure and its ligation with PD-L1 ligands expressed on tumor cells results in negative regulation of T cells [20]. Blocking of antibody mediated blockade of PD-1 or PD-L1 has been shown to enhance T cell activity with specificity for tumor cells [21].