Fig. 4

This figure illustrates the interactions of OSCC with NK cells and CD8 + T lymphocytes. The detection of cancer cells by NK cells and CD8 + T lymphocytes leads to the release of lytic enzymes and also anticancer cytokines, including TNF-α and IFN-γ. These cytokines not only induce apoptosis in OSCC cells but also trigger the expression of PD-L1. PD-L1 can bind to PD-1, leading to the exhaustion of NK cells and CD8 + T cells. The expression of CD155 by OSCC cells has a similar consequence. Radiotherapy and chemotherapy can also boost the release of TNF-α and IFN-γ by inducing immunogenic cell death in TME. However, exposure of NK cells and lymphocytes to radiation or chemotherapy drugs can induce apoptosis in these cells. Inhibiting the PD-L1-PD-1 axis or the CD155-TIGIT axis can prevent the exhaustion of NK cells and CD8 + T lymphocytes. In addition, treatment with IL-2 or IL-15 can increase the expression of NKG2D and the release of anticancer cytokines. (Casp: Caspase; ICIs: Immune checkpoint inhibitors; NKG2D: natural killer group 2, member D; TCR: T cell receptor; TIGIT: T cell immunoreceptor with Ig and ITIM domains; NF-κB: nuclear factor-κB; PD-1: Programmed death 1; PD-L1: Programmed death ligand 1; PI3K: Phosphoinositide 3-kinase; STAT: Signal transducer and activator of transcription)