Figure 2.

Biological activity of membrane and soluble PD-1/PD-L1 in tumor immunity. (A) The complete activation of T cells relies on two signals, with the first signal provided by the specific binding of T-cell receptor (TCR) to major histocompatibility complex (MHC) and the second signal provided by the interaction of CD28 on T cell surfaces with co-stimulatory molecules CD80/CD86 expressed by antigen-presenting cells (APCs). (B) The mechanism of PD-1/PD-L1 signaling involves the recruitment of the Src homology 2 domain containing phosphatases 2 (SHP2) to the PD-1 cytoplasmic domain, which dephosphorylates signaling molecules of the PI3K-AKT and MAPK pathways, thereby restricting T-cell proliferation, activation and survival. (C) sPD-1 has been found to suppress the interactions of PD-1 with PD-L1 and PD-L2 and the interaction of PD-L1 with CD80. However, sPD-1 may also have reverse signaling effects on APCs via the PD-L1/PD-L2 pathway and inhibits T cell function. (D) sPD-L1, like mPD-L1, binds to PD-1 to transmit negative regulatory signals.