Activation of stimulator of interferon genes (STING) and inhibition of vascular endothelial growth factor receptor (VEGFR) by telatinib induce antitumor activity[image]

TL;DR

This study shows that telatinib, a drug originally targeting VEGFR2, also activates the STING immune pathway, which could help fight cancer.

Contribution

Telatinib is shown to activate the STING pathway, offering a new mechanism for its antitumor activity.

Findings

Telatinib induces STING-dependent innate immune responses.

The crystal structure of STING with a telatinib analog was determined.

Telatinib's STING activation leads to antitumor effects in mice.

Abstract

The cGAS-STING signaling pathway is a crucial innate immune pathway that senses cytosolic DNA. Pharmacological activation of the cGAS-STING pathway might be a promising strategy for cancer immunotherapy. Here, we report that the cGAS-STING pathway is a new target of telatinib, an orally available vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor that has been investigated in clinical trials. In this study, we demonstrated that telatinib induced innate immune responses in a STING-dependent manner. In addition, we determined the crystal structure of STING bound to a telatinib analog, revealing the molecular interactions underlying STING activation. Moreover, we showed that telatinib-mediated STING activation contributed to the antitumor effects in tumor-bearing mouse models. In summary, our results reveal that telatinib, a previously identified VEGFR2 inhibitor, activates STING signaling, highlighting its potential in cancer immunotherapy.

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