| First Author | Schadt L | Year | 2019 |
| Journal | Cell Rep | Volume | 29 |
| Issue | 5 | Pages | 1236-1248.e7 |
| PubMed ID | 31665636 | Mgi Jnum | J:298560 |
| Mgi Id | MGI:6468838 | Doi | 10.1016/j.celrep.2019.09.065 |
| Citation | Schadt L, et al. (2019) Cancer-Cell-Intrinsic cGAS Expression Mediates Tumor Immunogenicity. Cell Rep 29(5):1236-1248.e7 |
| abstractText | Sensing of cytoplasmic DNA by cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) results in production of the dinucleotide cGAMP and consecutive activation of stimulator of interferon genes (STING) followed by production of type I interferon (IFN). Although cancer cells contain supra-normal concentrations of cytoplasmic DNA, they rarely produce type I IFN spontaneously. This suggests that defects in the DNA-sensing pathway may serve as an immune escape mechanism. We find that cancer cells produce cGAMP that is transferred via gap junctions to tumor-associated dendritic cells (DCs) and macrophages, which respond by producing type I IFN in situ. Cancer-cell-intrinsic expression of cGAS, but not STING, promotes infiltration by effector CD8(+) T cells and consequently results in prolonged survival. Furthermore, cGAS-expressing cancers respond better to genotoxic treatments and immunotherapy. Thus, cancer-cell-derived cGAMP is crucial to protective anti-tumor CD8(+) T cell immunity. Consequently, cancer-cell-intrinsic expression of cGAS determines tumor immunogenicity and makes tumors hot. These findings are relevant for genotoxic and immune therapies for cancer. |
