FIGURE 7.

Model of programmed cell death 1 (PD‐1)/programmed cell death‐ligand 1 (PD‐L1) axis in oral squamous cell carcinoma (OSCC) cells and CD8 T cell coculture. (A) CD8+ T cells recognize cancer cells through TCR binding with neo‐antigenic peptides, presented by MHC1 on the surface of OSCC cells. The activated cytotoxic T cells kill cancer cells either directly, through secreting cytotoxic granules containing perforin and granzymes, or indirectly, through releasing cytotoxic cytokines, such as IFNγ and TNF‐α. (B) Chronic arecoline exposure induces PD‐L1 upregulation on OSCC cells. When the PD‐1 expressed on T cell surface binds to PD‐L1 on OSCC cells, the PD‐1/PD‐L1 signaling exerts negative regulatory effects on TCR signaling and blunts the anti‐tumor function of CD8 T cells. Therefore, anti‐PD‐L1 antibody blocks the interaction of PD‐1 and PD‐L1 and abolishes the PD‐1/PD‐L1‐mediated inhibitory effects on CD8+ T cells, thus restoring the target cell‐killing effect