The following is a summary of “Context-dependent activation of STING-interferon signaling by CD11b agonists enhances anti-tumor immunity,” published in the June 2023 issue of the Cancer Cell by Liu et al.
Immunosuppressive tumors are characterized by chronic activation of inflammatory pathways and inhibition of interferon. Previous research has demonstrated that CD11b integrin agonists can enhance anti-tumour immunity by reprogramming myeloid cells, but the underlying mechanisms remain unknown. CD11b agonists alter tumor-associated macrophage (TAM) phenotypes by inhibiting NF-B signaling and activating interferon gene expression.
Repression of NF-B signaling is context-independent and entails degradation of the p65 protein. CD11b agonism, on the other hand, induces STING/STAT1 pathway-mediated interferon gene expression via FAK-mediated mitochondrial dysfunction, with the magnitude of induction dependent on the tumor microenvironment and amplified by cytotoxic therapies.
Researchers demonstrate that GB1275 treatment activates STING and STAT1 signaling in human tumor-associated macrophages (TAMs) using tissues from phase I clinical studies. These findings imply potential therapeutic strategies based on the mechanism of action of CD11b agonists and identify patient populations more likely to benefit.
Source: sciencedirect.com/science/article/pii/S1535610823001629
