Anti-PD-1/PD-L1 Therapy for Non-Small-Cell Lung Cancer: Toward Personalized Medicine and Combination Strategies

Figure 1

Effect of PD-1/PD-L1 signaling on major signaling pathways and reprograming in T cells. Upon the stimulation of antigen, the MHC on the surface of APC could present antigens to the TCR and promote TCR/CD3 chains to phosphorylate, resulting in an activation and recruitment of Lck and Zap-70, which in turn lead to the phosphorylation of tyrosine motifs (ITAM) and initiation of the downstream signaling cascade of TCR. However, in the pathological state, the PD-1 bind to its ligand PD-L1 or PD-L2; the tyrosine phosphatase SHP-2 or SHP-1 can be recruited and bind to the ITSM sequence in the PD-1 cytoplasmic tail. An activation of PD-L/PD-L1 signaling PD-1 mediates the inhibition of the PI3K/Akt and Ras/MEK/Erk signaling pathway, resulting in the inhibition of T cell proliferation, protein synthesis, survival, and IL-2 production. APC: antigen-presenting cell; HLA: human leukocyte antigen; TCR: T cell receptor.