Figure 4. (a) The regulation of PD-1/PD-L1 expression involves multiple pathways. The PI3K/AKT pathway, MAPK pathway, JAK/STAT pathway, WNT pathway, NF-κB pathway, and Hedgehog (Hh) pathway collectively stimulate the expression of the PD-1/PD-L1 axis. (b) Impact of PD-1/PD-L1 immune checkpoint engagement on T-cell fate. The interaction between PD-1 and PD-L1 triggers phosphorylation within PD-1's ITIMs and ITSMs, prompting the association with SHP-2 phosphatase. This interaction inhibits the PI3K/AKT and Ras/MAPK/ERK pathways, culminating in T-cell apoptosis.