Mitochondrial control of innate immune signaling by irradiated cancer cells

Abstract

Type I interferon (IFN) release by irradiated cancer cells is paramount for radiation therapy to elicit anticancer immunity. Our findings demonstrate that mitochondrial outer membrane permeabilization (MOMP) triggered by RT enables exposure of mitochondrial DNA to the cytosol, hence setting off CGAS-driven type I IFN synthesis. These data point to the existence of a therapeutically actionable mitochondrial checkpoint that restricts innate immune signaling in irradiated cancer cells.

Keywords

• abscopal responses
• autophagy
• caspases
• immunogenic cell death
• micronuclei
• sting
• venetoclax