Background and Aims

Background: Blockade of PD-L1 expression on tumor cells via anti–PD-L1 monoclonal antibody has shown great promise in cancer treatment, this drug is associated with immune-related adverse effects (irAEs). Studies showed that patients with PD-L1⁻ tumors respond favorably to anti–PD-L1 mAb therapy by inhibiting the PD-L1⁺ on NK cells, but simultaneously, directly inhibited CD8⁺ T cell proliferation in a PD-L1-dependent manner. They also shown that PD-L1 was upregulated by monocyte-derived IL-18. The organotellurium compound (Octa-O-bis-(R,R)-tartarate ditellurane (SAS)) has been shown previously to inhibit PD-L1⁺ in tumors and IL-18 by inhibition of caspase 1. SAS studies showed significant impact on decreasing irAEs.

Aims: The aim study was to evaluate the ability of SAS to decrease the level of PD-L1 on NK cells and found its impact on decreasing irAEs.

Methods

Methods: Mononuclear cells from peripheral blood and umbilical cord blood cells were incubated with tumor cell line (K562) and SAS or anti-IL-18. NK isolated from UCB with NK isolation kit were incubated as described. PD-L1 of NK cells (CD56⁺ CD3^-) were measured with FACS and analyzed with Flowjo.

Results

Results: Our results show that treatment of NK cells with AS101 results in a dose dependent decrease in PD-L1 in the presence and absence of MNC (IL-18 source) which was more significant than anti-IL-18 use.

Conclusions

Conclusions: The immunomodulator SAS can reduce PD-L1 in NK cells. In previous studies SAS exhibited ability to reduce PD-L1 on tumors. These results suggest that SAS might have a potential to treat cancer patient with PD-L1^- tumors.