Mitochondrial control of innate immune signaling by irradiated cancer cells
Takahiro Yamazaki, Lorenzo Galluzzi
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.
Topics & Concepts
Innate immune systemMitochondrionCytosolCancer cellImmune systemMitochondrial DNAImmunityInterferonCancer researchCancerDNA damageImmune checkpointBiologyCell biologyCancer immunotherapyImmunologyImmunotherapyChemistryDNAGeneBiochemistryGeneticsEnzymeinterferon and immune responsesImmune Response and InflammationImmune cells in cancer