ArticleCancer cell2021
DNA Sensing in Mismatch Repair-Deficient Tumor Cells Is Essential for Anti-tumor Immunity.
Article in Cancer cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 187 papers, 3 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
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Who cites it
187 citing papers in PubMed, 3 syntheses or guidelines pooled it, 269 citations in OpenAlex.
- Targeting DNA damage response to enhance cancer immunotherapy efficacy: molecular mechanisms and clinical advances.Medical oncology (Northwood, London, England) · 2025Pooled it
- Pooled it
- cGAS in nucleus: The link between immune response and DNA damage repair.Frontiers in immunology · 2022Pooled it
- Immunological biomarkers of response and resistance to treatment with cabozantinib and nivolumab in recurrent endometrial cancer.Journal for immunotherapy of cancer · 2025Trial
- Temozolomide Treatment Alters Mismatch Repair and Boosts Mutational Burden in Tumor and Blood of Colorectal Cancer Patients.Cancer discovery · 2022Trial
- Pembrolizumab versus chemotherapy for microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer (KEYNOTE-177): final analysis of a randomised, open-label, phase 3 study.The Lancet. Oncology · 2022Trial
- TREX1 limits anti-tumor immunity by degrading short cytosolic DNA molecules.EMBO reports · 2026Article
- Targeting WRN Helicase in Microsatellite-Instable Colorectal Cancer Induces Antitumor Immunity through Extrachromosomal Circular DNA Release.Cancer research · 2026Article
- Targeting WIP1 reprograms immunosuppressive tumor microenvironment to potentiate immunotherapy response in colorectal cancer.Cell death and differentiation · 2026Article
- Mismatch repair protein MLH1 controls testis development by regulating the Hippo-YAP signaling pathway.Nucleic acids research · 2026Article
- The DNA damage response and cancer immunotherapy.Nature reviews. Cancer · 2026Review
- The cGAS/STING pathway in cancer: translating innate DNA sensing into therapeutic potential.The Journal of clinical investigation · 2026Review
- Elevated TMC8 expression correlates with CD8Translational cancer research · 2026Article
- Divergent Roles of Canonical and Non-Canonical Mismatch Repair in Regulating Temozolomide Sensitivity in Glioblastoma.International journal of molecular sciences · 2026Review
- A DR5/Ligase 3-mediated feedback loop perpetuates immunogenicity in mismatch repair deficient colorectal cancer.Gastroenterology · 2026Article
- Tumor-draining lymph nodes shape the tumor microenvironment through enrichment of tumor-reactive effector-exhausted CD8Signal transduction and targeted therapy · 2026Article
- Advances in the management of metastatic gastric cancer: current strategies and emerging therapeutics.Nature reviews. Clinical oncology · 2026Review
- Striking the right balance with type I interferon signalling in cancer.Nature reviews. Cancer · 2026Review
- Current Status of the Diagnosis and Treatment of Mismatch Repair Deficient Colorectal Cancer.Biomedicines · 2026Review
- Accelerating tumor evolution and enhancing immunotherapy efficacy in lung adenocarcinoma based on EXO1 inhibition.Translational lung cancer research · 2026Article
127 more citing papers are in PubMed but not listed here.
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Authors and funding
26 authors at 4 institutions in 1 country.
Funding
Abstract
Increased neoantigens in hypermutated cancers with DNA mismatch repair deficiency (dMMR) are proposed as the major contributor to the high objective response rate in anti-PD-1 therapy. However, the mechanism of drug resistance is not fully understood. Using tumor models defective in the MMR gene Mlh1 (dMLH1), we show that dMLH1 tumor cells accumulate cytosolic DNA and produce IFN-β in a cGAS-STING-dependent manner, which renders dMLH1 tumors slowly progressive and highly sensitive to checkpoint blockade. In neoantigen-fixed models, dMLH1 tumors potently induce T cell priming and lose resistance to checkpoint therapy independent of tumor mutational burden. Accordingly, loss of STING or cGAS in tumor cells decreases tumor infiltration of T cells and endows resistance to checkpoint blockade. Clinically, downregulation of cGAS/STING in human dMMR cancers correlates with poor prognosis. We conclude that DNA sensing within tumor cells is essential for dMMR-triggered anti-tumor immunity. This study provides new mechanisms and biomarkers for anti-dMMR-cancer immunotherapy.
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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.