Figure 9: Graphical summary.
From: DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity
Left, treatment with a radiation regimen that causes dsDNA accumulation in the cancer cells cytosol without inducing the DNAse Trex1 activates interferon type-I pathway via cGAS/STING. Downstream recruitment of DC and activation of CD8+ T cells is enabled and tumour rejection occurs in synergy with anti-CTLA4 or anti-PD-1 antibody. Right, in tumour treated with a dose of radiation above the threshold for Trex1 induction dsDNA is cleared from the cytosol precluding interferon-β release by the cancer cells. This leads to insufficient DC recruitment and activation and lack of CD8+ T cell activation resulting in absence of local and abscopal tumour regression in combination with immune checkpoint inhibitors.
