Fig. 3

Blockade of CTLA-4, or PD-1, or PD-L1 signaling in tumor immunotherapy. The activation of T cells requires double signaling. The first signal of T cell activation comes from the specific binding of TCR to MHC. The second signal of T cell activation comes from costimulatory molecules, namely signals mediated by the interaction of APC-expressed costimulatory molecules with corresponding receptors or ligands on the T cell surface. Costimulatory molecules can be divided into positive co-stimulatory molecules and negative co-stimulatory molecules. CD28/B7 is an important positive co-stimulatory molecule, and CTLA-4, which is highly homologous to CD28 molecule, has a ligand of B7, but the binding of CTLA-4 and B7 mediates the conduction of negative signals. Anti-CTLA-4 maintains T cell activation by blocking the transmission of inhibitory signals by inhibiting the binding of CTLA-4 to CD80 or CD86 molecules. When T cells kill tumor cells, the combination of PD-L1 expressed on tumor cells and PD-1 expressed on T cells will transmit negative regulatory signals to T cells, causing T cells to be unable to recognize cancer cells and tumor cells to achieve “immune escape”. Anti-PD-1 or anti-PD-L1 prevents PD-L1 from binding to PD-1, thereby reactivating T cells to kill tumors