cyclic-guanosine-monophosphate-adenosine-monophosphate and Colonic-Neoplasms

DNA sensing by the STING pathway is emerging to be a crucial component of the antitumor immune response. Although it plays a key role in the activation of tumor immune cells, exactly how STING is activated by tumor cells is not fully understood. Recent evidence suggests that cGAS can be directly engaged and produces 2'3'-cyclic-GMP-AMP (cGAMP) within certain tumor cells upon stimulation with DNA damaging agents. Because cGAMP can transfer between adjacent cells, the capacity of tumor cells to produce cGAMP may activate tumor immune cells, even in the absence of functional STING signaling within the tumor. Here we describe a simple coculture protocol allowing for the functional characterization of cGAS/STING activity in tumor cells, together with cGAMP transfer to adjacent cells. This approach will help define how different tumors engage the STING pathway, and whether synthetic STING agonists should be used to potentiate the antitumor effects of chemotherapies.

Topics: Coculture Techniques; Colonic Neoplasms; Humans; Membrane Proteins; Nucleotides, Cyclic; Nucleotidyltransferases; Tumor Cells, Cultured

Stimulator of interferon genes (STING) is a receptor in the endoplasmic reticulum that propagates innate immune sensing of cytosolic pathogen-derived and self DNA

Topics: Animals; Benzimidazoles; Colonic Neoplasms; Drug Design; Humans; Ligands; Membrane Proteins; Mice; Models, Molecular; Nucleotides, Cyclic