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Telomere Stress Potentiates STING-Dependent Anti-tumor Immunity
- Source :
- Cancer Cell
- Publication Year :
- 2019
-
Abstract
- Summary 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.
- Subjects :
- 0301 basic medicine
Cancer Research
Telomerase
DNA damage
medicine.medical_treatment
Biology
Adaptive Immunity
CD8-Positive T-Lymphocytes
Article
03 medical and health sciences
0302 clinical medicine
Interferon
Immunity
Cell Line, Tumor
Neoplasms
medicine
Animals
Humans
Mice, Knockout
Mice, Inbred BALB C
Thionucleosides
Deoxyguanosine
Membrane Proteins
Immunotherapy
Neoplasms, Experimental
Telomere
HCT116 Cells
Immunity, Innate
Tumor Burden
Mice, Inbred C57BL
030104 developmental biology
Oncology
030220 oncology & carcinogenesis
Humanized mouse
Cancer cell
Cancer research
medicine.drug
Signal Transduction
Subjects
Details
- ISSN :
- 18783686
- Volume :
- 38
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Cancer cell
- Accession number :
- edsair.doi.dedup.....0f063176c0ca8a67e087cb11046ee83e