ArticleThe EMBO journal2021
5-Fluorouracil efficacy requires anti-tumor immunity triggered by cancer-cell-intrinsic STING.
Article in The EMBO journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
66 citing papers in PubMed, 109 citations in OpenAlex.
- FBXW5 blunts RIGI/MDA5/IFN signaling to drive immune evasion and chemo-immune resistance in triple-negative breast cancer models.The Journal of clinical investigation · 2026Article
- TFAM loss drives oxaliplatin resistance by linking mtDNA release to STING-TBK1-mediated lysophagy.Oncogene · 2026Article
- Ribonucleotides Amplify Mitochondrial DNA-Driven cGAS-STING Activation via FdUMP-ribonucleotide Hybrid Particles to Potentiate Chemoimmunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Engineered probiotics for tumor-targeted combination chemoimmunotherapy.Science translational medicine · 2026Article
- Targeting PID1 generates oxysterols to switch macrophage cell fates for improved antitumor immunity.Nature cancer · 2026Article
- 5-FU chemotherapy induces functional CD7Science China. Life sciences · 2026Article
- Context-dependent actions of STING pathway in colitis and associated colon cancer.Genes & diseases · 2026Review
- Cell Line-Dependent Effects of Spheroid Formation Method on Drug Response in Melanoma Models.Cells · 2026Article
- Subcellular Redistribution of Endomembrane GPR15 Promotes NAD+-Mediated Metabolic Reprogramming and Boosts 5-FU Chemosensitivity in Colorectal Cancer.Cancer research · 2026Article
- Targeting the DDX3/PAF1 axis enhances chemotherapy efficacy in pancreatic ductal adenocarcinoma.Cancer letters · 2026Article
- Programmed cell death in lung cancer: mechanisms, immune responses, and therapeutics.Apoptosis : an international journal on programmed cell death · 2026Review
- TBKBP1 induces capecitabine resistance through negative regulation of type I interferon pathway in triple-negative breast cancer.Oncogene · 2026Article
- Case Report: Long-term disease control with immunotherapy in primary mandibular adenoid cystic carcinoma presenting with pulmonary metastasis.Frontiers in immunology · 2026Article
- CCR-CCL axes as key upstream influencers of pancreatic ductal adenocarcinoma: CCR2-CCL2, CCR5-CCL5, CCR4-CCL17/22, CCR6-CCL20, CCR7-CCL19/21.Frontiers in immunology · 2026Review
- Targeting VCP enhances colorectal cancer therapy through STING stabilization.Journal for immunotherapy of cancer · 2025Article
- Chronic ISG15 Exposure Accelerates CD8+ T-cell Dysfunction while Increasing PD-1 Blockade Sensitivity in Oral Squamous Cell Carcinoma.Cancer immunology research · 2025Article
- The cGAS‒STING pathway in colorectal cancer: bridging innate immunity and therapeutic strategies.Journal of experimental & clinical cancer research : CR · 2025Review
- cGAS-STING signaling in melanoma: regulation and therapeutic targeting.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Article
- Emerging Strategies for Targeting Angiogenesis and the Tumor Microenvironment in Gastrointestinal Malignancies: A Comprehensive Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
6 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
5-Fluorouracil (5-FU) is a widely used chemotherapeutic drug, but the mechanisms underlying 5-FU efficacy in immunocompetent hosts in vivo remain largely elusive. Through modeling 5-FU response of murine colon and melanoma tumors, we report that effective reduction of tumor burden by 5-FU is dependent on anti-tumor immunity triggered by the activation of cancer-cell-intrinsic STING. While the loss of STING does not induce 5-FU resistance in vitro, effective 5-FU responsiveness in vivo requires cancer-cell-intrinsic cGAS, STING, and subsequent type I interferon (IFN) production, as well as IFN-sensing by bone-marrow-derived cells. In the absence of cancer-cell-intrinsic STING, a much higher dose of 5-FU is needed to reduce tumor burden. 5-FU treatment leads to increased intratumoral T cells, and T-cell depletion significantly reduces the efficacy of 5-FU in vivo. In human colorectal specimens, higher STING expression is associated with better survival and responsiveness to chemotherapy. Our results support a model in which 5-FU triggers cancer-cell-initiated anti-tumor immunity to reduce tumor burden, and our findings could be harnessed to improve therapeutic effectiveness and toxicity for colon and other cancers.
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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.