Telomere Stress Potentiates STING-Dependent Anti-tumor Immunity

Ilgen Mender, Anli Zhang, Zhenhua Ren, Chuanhui Han, Yafang Deng, Silvia Siteni, Huiyu Li, Jiankun Zhu, Aishwarya Vemula, Jerry W. Shay, Yang Xin Fu

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)400-411.e6
JournalCancer Cell
Issue number3
StatePublished - Sep 14 2020


  • 6-thio-dG
  • DNA damage
  • PD-1/PD-L1
  • anti-tumor immunity
  • checkpoint blockade
  • immunotherapy
  • innate sensing
  • telomerase
  • telomere-targeting therapy

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research


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