ArticleCancer discovery2024
TREX1 Inactivation Unleashes Cancer Cell STING-Interferon Signaling and Promotes Antitumor Immunity.
Article in Cancer discovery, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 87 citations in OpenAlex.
- TREX1 limits anti-tumor immunity by degrading short cytosolic DNA molecules.EMBO reports · 2026Article
- The cGAS-STING/MITA pathway in innate antiviral immunity and beyond.Cell insight · 2026Review
- The cGAS-STING pathway: mechanistic basis, dual biological functions and translational therapeutic advances.Apoptosis : an international journal on programmed cell death · 2026Review
- The bidirectional immunoregulatory effects of Traditional Chinese Medicine on the cGAS-STING signaling pathway and their translational prospects.Chinese medicine · 2026Review
- Review
- Immune response to DNA and RNA: structural insights, molecular mechanisms, and therapeutic targeting.Molecular biomedicine · 2026Review
- Dual-engineering metalloimmunotherapy mediatesBioactive materials · 2026Article
- Elevated TMC8 expression correlates with CD8Translational cancer research · 2026Article
- Targeting E3 ubiquitin ligases: Mechanistic breakthroughs and novel clinical translation pathways for tumor radioimmunotherapy.Molecular cancer · 2026Review
- Molecular mechanisms regulating cGAS/STING activation in health and disease.The Journal of clinical investigation · 2026Review
- Selective targeting of human TREX1 exonuclease by small molecule inhibitors is mediated by a conformational switch.NAR molecular medicine · 2026Article
- Chemotherapeutic induction of cytosolic single-stranded DNA accumulation sensitizes triple-negative breast cancer to immunotherapy.Journal for immunotherapy of cancer · 2026Article
- Rational design of a V-shaped DNA-targeted photosensitizer enables endogenous DNA damage-driven cGAS-STING activation and systemic antitumor immunity.Materials today. Bio · 2026Article
- Striking the right balance with type I interferon signalling in cancer.Nature reviews. Cancer · 2026Review
- Loss of the autoimmune risk gene TREX1 reveals a convergence of mechanisms promoting immune tolerance loss and antitumor immunity.Science advances · 2026Article
- PTPN2 inhibition unleashes response to STING agonism in head and neck squamous cell cancer.Nature communications · 2026Article
- Interferon stimulatory DNA activates the DNA damage signaling through ATM and DNA-PK sensing.The Journal of biological chemistry · 2026Article
- Therapy-induced remodeling of the tumor immune microenvironment: Mechanistic insights and implications for immunotherapy.Chinese medical journal · 2026Review
- Vascular STING activation facilitates NK cell anti-tumor immunity in small cell lung cancer.Cancer cell · 2026Article
- Fasting-mimicking diet induces IFNβ secretion in tumor-associated macrophages via NRF1-mediated ubiquitin-dependent proteolysis of Trex1.British journal of cancer · 2026Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
27 authors at 4 institutions in 2 countries.
Funding
Abstract
A substantial fraction of cancers evade immune detection by silencing Stimulator of Interferon Genes (STING)-Interferon (IFN) signaling. Therapeutic reactivation of this program via STING agonists, epigenetic, or DNA-damaging therapies can restore antitumor immunity in multiple preclinical models. Here we show that adaptive induction of three prime exonuclease 1 (TREX1) restrains STING-dependent nucleic acid sensing in cancer cells via its catalytic function in degrading cytosolic DNA. Cancer cell TREX1 expression is coordinately induced with STING by autocrine IFN and downstream STAT1, preventing signal amplification. TREX1 inactivation in cancer cells thus unleashes STING-IFN signaling, recruiting T and natural killer (NK) cells, sensitizing to NK cell-derived IFNγ, and cooperating with programmed cell death protein 1 blockade in multiple mouse tumor models to enhance immunogenicity. Targeting TREX1 may represent a complementary strategy to induce cytosolic DNA and amplify cancer cell STING-IFN signaling as a means to sensitize tumors to immune checkpoint blockade (ICB) and/or cell therapies. SIGNIFICANCE: STING-IFN signaling in cancer cells promotes tumor cell immunogenicity. Inactivation of the DNA exonuclease TREX1, which is adaptively upregulated to limit pathway activation in cancer cells, recruits immune effector cells and primes NK cell-mediated killing. Targeting TREX1 has substantial therapeutic potential to amplify cancer cell immunogenicity and overcome ICB resistance. This article is featured in Selected Articles from This Issue, p. 695.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.