Advances in Immunotherapy for Glioblastoma Multiforme

Figure 1

Mechanism of CTLA-4 and PD-L1 immune checkpoints. The CTLA-4 immune checkpoint (left figure) occurs early during the priming phase of the immune response, acting within secondary lymphoid organs. CTLA-4 is a powerful inhibitory T-cell receptor that can preferentially bind to CD80/CD86 on the surface of APCs, preventing their binding to the T-cell costimulatory receptor CD28, thus leading to decreased T-cell activation and proliferation in the context of antigen-presenting MHC class I. PD-1 signaling takes place during the effector phase of the immune responses within the tumor microenvironment. The inhibitory PD-1 T-cell receptor interacts with one of two currently identified PD-1 ligands: PD-L1 or PD-L2, expressed on the surface of tumor cells. Engagement of PD-1 ligands with the PD-1, in the context of tumor antigen-presenting MHC class I, can decrease the T-cell tumor lytic capacity and induces T-cell anergy. APC: antigen-presenting cell.