ArticleCancer cell2021
MLH1 Deficiency-Triggered DNA Hyperexcision by Exonuclease 1 Activates the cGAS-STING Pathway.
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 152 papers, 2 of them syntheses that pooled it.
What it found
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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
152 citing papers in PubMed, 2 syntheses or guidelines pooled it, 228 citations in OpenAlex.
- Predictive value of PD-L1 expression and dMMR/pMMR status for immune checkpoint inhibitor combined with chemotherapy in advanced/recurrent endometrial cancer: a meta-analysis.World journal of surgical oncology · 2026Pooled it
- cGAS in nucleus: The link between immune response and DNA damage repair.Frontiers in immunology · 2022Pooled it
- 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
- 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
- Combination immunotherapy for colorectal cancer: Clinical applications, rationale, challenges, and future perspectives.Cell reports. Medicine · 2026Review
- AK5 suppresses breast cancer progression and modulates anti-PD-L1 efficacy via the miR-182-5p/PD-L1 axis.iScience · 2026Article
- Review
- Methodological Landscape of DNA Damage Response Detection: From Conventional Assays to Future Innovations.Current issues in molecular biology · 2026Review
- Low-dose radiotherapy remodels the tumor immune microenvironment via the cGAS-STING pathway: mechanisms, challenges, and combination therapy strategies.Molecular cancer · 2026Review
- Calibrating the RT-cGAS-STING axis to drive cold-to-hot tumor transformation: mechanistic foundations and translational strategies for combination with immunotherapy.Molecular cancer · 2026Review
- Opportunities and challenges of targeting cGAS-STING in cancer.Nature reviews. Cancer · 2026Review
- ISGylation prevents autophagic degradation of STING and promotes antitumor immunity in lung cancer.Cell death & disease · 2026Article
- CDK10 inhibits innate sensing to constrain antitumor immunity.Nature cancer · 2026Article
- Memory B cell subset shapes antitumor immunity and response to PD-1 blockade in mismatch repair-deficient colorectal cancers.Journal for immunotherapy of cancer · 2026Article
- Rational modulation of immune mechanisms synergizes the anti-tumor effects of targeted radiation therapy in pre-clinical models.Frontiers in immunology · 2026Article
- Negative regulators antagonizing antitumor innate immune pathways in lung cancer immune evasion.Frontiers in immunology · 2026Review
- Innate immunity in tumour immunoediting and immunosurveillance.The EMBO journal · 2026Review
- Defining treatment-resistant brain cancer: Genetic screening to identify oncogene-driven immunomodulation and therapy resistance.Cancer gene therapy · 2026Review
92 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 5 institutions in 1 country.
Funding
Abstract
Tumors with defective mismatch repair (dMMR) are responsive to immunotherapy because of dMMR-induced neoantigens and activation of the cGAS-STING pathway. While neoantigens result from the hypermutable nature of dMMR, it is unknown how dMMR activates the cGAS-STING pathway. We show here that loss of the MutLα subunit MLH1, whose defect is responsible for ~50% of dMMR cancers, results in loss of MutLα-specific regulation of exonuclease 1 (Exo1) during DNA repair. This leads to unrestrained DNA excision by Exo1, which causes increased single-strand DNA formation, RPA exhaustion, DNA breaks, and aberrant DNA repair intermediates. Ultimately, this generates chromosomal abnormalities and the release of nuclear DNA into the cytoplasm, activating the cGAS-STING pathway. In this study, we discovered a hitherto unknown MMR mechanism that modulates genome stability and has implications for cancer therapy.
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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.