Disulfiram/copper triggers cGAS-STING innate immunity pathway via ROS-induced DNA damage that potentiates antitumor response to PD-1 checkpoint blockade.

ABSTRACT: Immune checkpoint blockades (ICBs) have emerged as the leading strategy for treating advanced malignancies; however, their clinical efficacy is frequently constrained by primary or acquired resistance. Harnessing innate immune signaling to increase lymphocyte infiltration into tumors has been recognized a promising approach to augment the anti-cancer immune response to ICBs. Disulfiram (DSF), an FDA-approved drug for chronic alcoholism, has shown potent anti-tumor effect, particularly when used in combination with copper (Cu). Here, we demonstrated a combination treatment of DSF and Cu (DSF/Cu) robustly activated cancer cell-intrinsic cGAS-STING-dependent innate immune signaling pathway. Further studies revealed that DSF/Cu caused mitochondrial and nuclear DNA damage and the release of cyt

SUBMITTER: Yuan M 

PROVIDER: S-EPMC11844283 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature