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. 2021 Apr 28;12:679117. doi: 10.3389/fimmu.2021.679117

Figure 2.

Figure 2

NK cells interact with the PD-1/PD-L1 immune checkpoint axis. NK cells can increase the expression of PD-L1 on tumor cells through release of cytokines such as IFN-γ, promoting PD-1/PD-L1 driven stimulation of Treg production which in turn can inhibit NK cell function. 1) NK cells have also been shown to express both PD-L1 and PD-1 themselves. PD-L1 expression can be induced in NK cells by direct interaction with tumor cells via the p38/NF-κB pathway and by stimulation with cytokines IL-12 and IL-18 (25). 2) PD-1 expression in NK cells has been shown to be upregulated in a variety of cancers (26, 60, 61) and to be inducible in response to IL-2 stimulation (60) and glucocorticoid signaling (62). 3) Treatment with PD-1/PD-L1 blockade therapy can help prevent Treg inhibition of NK cells and counteract PD-1/PD-L1 driven NK cell dysfunction. 4) PD-L1 expression on tumors correlates with response to PD-1/PD-L1 checkpoint blockade therapies, thus induction of PD-L1 by NK cells should improve outcomes of this treatment.