PPT1 is a negative regulator of STING signaling in cancer cells and its inhibition reactivates immune surveillance in cold tumors.

ABSTRACT: Immunotherapy modalities have revolutionized cancer treatment for a number of metastatic and treatment-refractory tumor types. Still, many malignancies that lack T cell infiltration and are termed immunologically "cold" fail to respond to these modalities. One approach to increase tumor immunogenicity has been to induce stimulator of interferon gene (STING) and downstream interferon signaling that is often dysregulated in cold tumors. Despite some early success of STING agonists in preclinical cancer models, these approaches have not been successful in the clinic due to poor tumor penetrance and systemic toxicities. Here, we performed a genome-wide CRISPR screen to uncover therapeutic targets to activate STING expression in human tumors. We identified the lysosomal hydrolase Palmitoyl Prot

SUBMITTER: Chowdhury SR 

PROVIDER: S-EPMC12501185 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature