The Tellurium compound SAS decreases PD-L1 protein expression on melanoma cells and in mice models: mechanisms of action and clinical

SAS is an organotellurium compound with multifaceted immunoregulatory properties that is remarkable for its lack of toxicity .the therapeutic effect of SAS had been tested in our lab on murine B-16 melanoma cells and c57BL male mice.

Among the inhibitory immune mediators that plays an important role in the maintenance of peripheral tolerance are pd-1 receptor (programed death 1) and its ligand pdl-1.

Some cancer cells may benefit from the PD-1:PDL-1 pathway interaction -

PDL-1expressed on tumor cell surface interacts with PD-1 receptor expressed on CD8+ T cells leads to T cells anergy preventing their functions against tumor cells. In addition Some studies reveling a potential linkage between chemotherapy and immunoresistance through activation of ERK pathway that leads to overexpression of PDL-1 .

Therefore inhibition of one or more of these immune checkpoints may play an important role in the future of immunotherapy.

In this work we show how the tellurium compound SAS inhibits PD-L1 -activity was exerted via the inactivation of the VLA-4/ p-Akt/ NFkB axis .In our result in B-16 melanoma cells we show that The compound also has the ability of inhibiting intracellular expression and secretion of the anti-inflammatory cytokine IL-10(Interleukin 10). Moreover, we found that SAS mediates B16 cells death caused by CD8 + T cells in a significant death rate of about 75% of cells using FACS analysis.

In VIVO treatment with SAS in a mouse model of B16 melanoma, resulted in tumor shrinkage due to PD-L1 inhibition. Furthermore, combination therapy with SAS and anti PD-1 resulted in an additive effect or even synergistic.

The results suggest that the tellurium compound SAS could be useful as a therapeutic approach for immunotherapy in melanoma.