Targeting redox metabolism and low-dose radiotherapy synergistically activate cGAS-STING pathway to improve NK cell therapy efficacy in hepatocellular carcinoma - PubMed
4 hours ago
- #NK cell therapy
- #cGAS-STING pathway
- #Hepatocellular carcinoma
- Adoptive NK cell therapy (ANKCT) is a promising treatment for hepatocellular carcinoma (HCC), but its efficacy is limited by insufficient NK cell homing and immunosuppressive M2-polarized tumor-associated macrophages (TAMs).
- Activation of the cGAS-STING pathway enhances NK-cell recruitment and reprograms TAMs toward a proinflammatory M1 phenotype.
- Low-dose radiotherapy (LDRT) activates the cGAS-STING pathway via ROS-mediated DNA damage but is hindered by HCC's robust antioxidant systems (Trx and GSH).
- A biomimetic nanoparticle (A@MMOF) was developed to disrupt tumor redox homeostasis by inhibiting GSH and Trx, amplifying ROS levels, and synergizing with LDRT to activate the cGAS-STING pathway.
- A@MMOF combined with LDRT remodels the tumor microenvironment, enhances NK cell infiltration and activation, and improves ANKCT efficacy in HCC.