Summary

The cGAS-STING pathway can be activated by radiation induced DNA damage and because of its important role in anti-cancer immunity activation, methods to increase its activation in cancer cells could provide significant therapeutic benefits for patients. We explored the impact of hafnium oxide nanoparticles (NBTXR3) activated by radiotherapy on cell death, DNA damage, and activation of the cGAS-STING pathway. We demonstrate that NBTXR3 activated by radiotherapy enhances cell destruction, DNA double strand breaks, micronuclei formation and cGAS-STING pathway activation in a human colorectal cancer model, compared to radiotherapy alone.

Summary

Recent studies reported that radiotherapy could activate the cGAS-STING pathway, which plays a fundamental role in the immune response to cytoplasmic DNA, by activation of the transcriptional factor IRF3, leading to expression of interferon-beta. Moreover, cGAS-STING activation appears to be an important component for tumor resident Antigen-Presenting Cells activation, a crucial step for induction of CD8+ T cell response against tumor derived antigens.

In this study, it was observed the ability of radiotherapy-activated NBTXR3 to increase cGAS-STING pathway response, compared to radiotherapy alone.