Activation of the cGAS-STING pathway begins by recognition of cytoplasmic dsDNA by cGAS which then generates the natural ligand of STING, 2’3’ cGAMP

ENPP1 negatively regulates this pathway by breaking down 2’3’ cGAMP into AMP and GMP

AMP can be converted by CD73 into Adenosine, a key immune suppressive molecule in the tumor microenvironment

ENPP1 is highly upregulated as tumors becomes metastatic

High levels of ENPP1 have been correlated with:

• Reduced immune infiltration

• Increased metastasis

• Tumor resistance to chemotherapy and adaptive immunotherapies