| First Author | Mender I | Year | 2020 |
| Journal | Cancer Cell | Volume | 38 |
| Issue | 3 | Pages | 400-411.e6 |
| PubMed ID | 32619407 | Mgi Jnum | J:296313 |
| Mgi Id | MGI:6466850 | Doi | 10.1016/j.ccell.2020.05.020 |
| Citation | Mender I, et al. (2020) Telomere Stress Potentiates STING-Dependent Anti-tumor Immunity. Cancer Cell 38(3):400-411.e6 |
| abstractText | Telomerase is an attractive target for anti-tumor therapy as it is almost universally expressed in cancer cells. Here, we show that treatment with a telomere-targeting drug, 6-thio-2'-deoxyguanosine (6-thio-dG), leads to tumor regression through innate and adaptive immune-dependent responses in syngeneic and humanized mouse models of telomerase-expressing cancers. 6-thio-dG treatment causes telomere-associated DNA damages that are sensed by dendritic cells (DCs) and activates the host cytosolic DNA sensing STING/interferon I pathway, resulting in enhanced cross-priming capacity of DCs and tumor-specific CD8(+) T cell activation. Moreover, 6-thio-dG overcomes resistance to checkpoint blockade in advanced cancer models. Our results unveil how telomere stress increases innate sensing and adaptive anti-tumor immunity and provide strong rationales for combining telomere-targeting therapy with immunotherapy. |
