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. Author manuscript; available in PMC: 2021 Aug 1.
Published in final edited form as: Drug Discov Today. 2020 Jun 17;25(8):1521–1527. doi: 10.1016/j.drudis.2020.06.008

Figure 2.

Figure 2.

Phosphodiesterase 5 (PDE5) and PDE10 inhibition suppress tumor immunity. PDE5 and PDE10 inhibition increase intracellular cGMP levels to activate PKG that phosphorylates β-catenin (B-CAT) to induce ubiquitination and proteasomal degradation of B-CAT, thereby suppressing Tcf/Lef-mediated gene transcription that results in direct killing of cancer cells as well as greater cytotoxic T cell infiltration to the tumor site by decreasing the immunosuppressive activity of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), therefore enhancing the immunogenic milieu within the tumor microenvironment. cGMP is physiologically induced by guanylyl cyclases (GC) and acts in concert with cGMP PDE inhibitors to increase intracellular cGMP levels.