Figure 3.

PD-1/PDL-1-dependent pathway: PD-1 expressed on the activated T cells. The receptor-ligand interaction induces an inhibitory antitumor activity. Whereas the administration of anti-PD1 counter the inhibitory anti-tumor response and unleash the T-cell activity by upregulating the T-cell activation and proliferation by enhancing effector function. Therefore, the T-cell receptor binds with the MHC molecule on APC and releases the perforin and granzyme for tumor death. CTLA-4-dependent pathway: Anti CTLA4: the anti-CTLA4 blocked the CTLA4, when bound with the Fc receptor on APC and induce antibody-dependent cellular toxicity. Though the higher expression of CTLA4 on CD4+, CD25+, and T regulatory cells make them prone to anti-CTLA4 induced cellular toxicity. Anti- CTLA-4 can binds to CTLA4 on the surface of Treg cells, preventing it from counter-regulating T-cell activation via CD28-mediated co-stimulatory pathways. By blocking CTLA4 on the surface of activated conventional T cells, -CTLA4 can increase T-cell responses. LAG-3-dependent pathway: The activity of LAG3: the activation of dendritic cells depends on the soluble LAG3 followed by MHC class II molecule signaling in lipid rafts microdomain. Furthermore, the mature dendritic cells induce the production of IL-12 and expression of CCR7 which allows migrating in the T-cells region followed by activation of T cells. The maturation and differentiation of T cells followed by tumor cell death