The combination of bezafibrate plus anti-PD-L1 reached synergistic tumoricidal effect in LLC xenograft mouse models, even though bezafibrate alone had no effect on tumor growth.
We also detected downregulation of PD-L1 in FXR-overexpressing Lewis lung carcinoma (LLC) mouse syngeneic models, indicating an FXR<sup>high</sup>PD-L1<sup>low</sup> subtype in which FXR suppresses tumor-infiltrating immune cells.
In Lewis lung carcinoma (LLC) and CMT167 models, dual inhibition of COX-2 and EGFR by melafolone promoted survival, tumor growth inhibition, and vascular normalization, and ameliorated CD8<sup>+</sup> T-cell suppression, accompanied by the downregulation of transforming growth factor-<i>β</i> (TGF-<i>β</i>), vascular endothelial growth factor (VEGF), and PD-L1 in the tumor cells.
Here, we report on the in vivo characterization of the anti-cancer activity of IL2-F8-TNF<sup>mut</sup> in four immunocompetent murine models of cancer, CT26, WEHI-164, F9 teratocarcinoma and Lewis lung carcinoma (LLC), using the product alone or in combination with a monoclonal antibody specific to murine PD-L1.