FOCUS on boosting tumor immunogenicity. In a paper just out in PNAS, researchers at UMass Chan Medical School report that PPT1 (Palmitoyl Protein Thioesterase 1) is a negative regulator of STING signaling in cancer cells. They showed that PPT1 is highly expressed in cold ovarian and prostate tumors. Pharmacological suppression of PPT1 using GNS561 increased STING stability and downstream signaling, leading to increased T cell migration. In ovarian and prostate cancer models treatment with GNS561 resulted in infiltration and activation of cytotoxic T cells, which turned “cold” tumors “hot” and reduced tumor growth, fibrosis, and dissemination without toxicity. Thus PPT1 inhibition may be a promising approach to activate STING and reactivate immune surveillance in “cold” tumors.
