The DOI matches its Crossref record; 66 of the 66 references it cites were found in a registry or an index.
Cancer-Cell-Intrinsic cGAS Expression Mediates Tumor Immunogenicity
Open accessAbstract
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.
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Cites
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Molecular Mechanisms of Radiation-Induced Cancer Cell Death: A Primer
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Metadata
- Authors
- Schadt, L., Sparano, C., Schweiger, N. A., Silina, K., Cecconi, V., Lucchiari, G., Yagita, H., Guggisberg, E., Saba, S., Nascakova, Z., Barchet, W., & van den Broek, M.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2019-10
- Volume
- 29
- Issue
- 5
- Pages
- 1236-1248.e7
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W2982425966
- Cited by
- 298
- References
- 66
- FWCI
- 11.46
- Type
- journal article
- Language
- en
- Open access
- gold
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- Schadt, L., Sparano, C., Schweiger, N. A., Silina, K., Cecconi, V., Lucchiari, G., Yagita, H., Guggisberg, E., Saba, S., Nascakova, Z., Barchet, W., & van den Broek, M. (2019). Cancer-Cell-Intrinsic cGAS Expression Mediates Tumor Immunogenicity. Cell Reports. https://doi.org/10.1016/j.celrep.2019.09.065
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