ArticleCancer research2022
ATM Regulates Differentiation of Myofibroblastic Cancer-Associated Fibroblasts and Can Be Targeted to Overcome Immunotherapy Resistance.
Article in Cancer research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 29 citations in OpenAlex.
- NOTCH3 regulates myofibroblastic CAF differentiation via the P62-ROS signaling axis to promote bladder cancer progression.Journal of experimental & clinical cancer research : CR · 2026Article
- Colony-stimulating factor-2 triggers NNMT-dependent myofibroblast activation in head and neck cancer.Oncogene · 2026Article
- Review
- Distinct mechanisms of replication stress induced by oncogenic RAS and cyclin E1 converge on R-loop-dependent fork reversal.Nature communications · 2026Article
- Single-cell analysis reveals the prognostic role of immune escape in the colorectal cancer microenvironment.Translational cancer research · 2026Article
- Pancreatic cancer-associated myofibroblasts: a review.International journal of biological sciences · 2026Review
- Article
- Medicinal chemistry breakthroughs on ATM, ATR, and DNA-PK inhibitors as prospective cancer therapeutics.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- Hidden forces: the impact of cancer-associated fibroblasts on non-small cell lung cancer development and therapy.Journal of translational medicine · 2025Review
- Unlocking the crucial role of cancer-associated fibroblasts in tumor metastasis: Mechanisms and therapeutic prospects.Journal of advanced research · 2025Review
- Redox Mechanisms Driving Skin Fibroblast-to-Myofibroblast Differentiation.Antioxidants (Basel, Switzerland) · 2025Article
- Identification and validation of biomarkers related to ferroptosis in idiopathic pulmonary fibrosis.Scientific reports · 2025Article
- Cancer-associated fibroblasts, tumor and radiotherapy: interactions in the tumor micro-environment.Journal of experimental & clinical cancer research : CR · 2024Review
- Cancer-associated fibroblasts: a versatile mediator in tumor progression, metastasis, and targeted therapy.Cancer metastasis reviews · 2024Review
- ZEB1-mediated fibroblast polarization controls inflammation and sensitivity to immunotherapy in colorectal cancer.EMBO reports · 2024Article
- Development and validation of a programmed cell death index to predict the prognosis and drug sensitivity of gastric cancer.Frontiers in pharmacology · 2024Article
- Reclassify High-Grade Serous Ovarian Cancer Patients Into Different Molecular Subtypes With Discrepancy Prognoses and Therapeutic Responses Based on Cancer-Associated Fibroblast-Enriched Prognostic Genes.Biomedical engineering and computational biology · 2024Article
- Review
- Article
- NADPH oxidase 4 is dispensable for skin myofibroblast differentiation and wound healing.Redox biology · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors at 5 institutions in 3 countries.
Funding
Abstract
Myofibroblastic cancer-associated fibroblast (myoCAF)-rich tumors generally contain few T cells and respond poorly to immune-checkpoint blockade. Although myoCAFs are associated with poor outcome in most solid tumors, the molecular mechanisms regulating myoCAF accumulation remain unclear, limiting the potential for therapeutic intervention. Here, we identify ataxia-telangiectasia mutated (ATM) as a central regulator of the myoCAF phenotype. Differentiating myofibroblasts in vitro and myoCAFs cultured ex vivo display activated ATM signaling, and targeting ATM genetically or pharmacologically could suppress and reverse differentiation. ATM activation was regulated by the reactive oxygen species-producing enzyme NOX4, both through DNA damage and increased oxidative stress. Targeting fibroblast ATM in vivo suppressed myoCAF-rich tumor growth, promoted intratumoral CD8 T-cell infiltration, and potentiated the response to anti-PD-1 blockade and antitumor vaccination. This work identifies a novel pathway regulating myoCAF differentiation and provides a rationale for using ATM inhibitors to overcome CAF-mediated immunotherapy resistance. SIGNIFICANCE: ATM signaling supports the differentiation of myoCAFs to suppress T-cell infiltration and antitumor immunity, supporting the potential clinical use of ATM inhibitors in combination with checkpoint inhibition in myoCAF-rich, immune-cold tumors.
Indexed as
Identifiers
What OpenQuestion holds
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.