ArticleProceedings of the National Academy of Sciences of the United States of America2017
Manipulating DNA damage-response signaling for the treatment of immune-mediated diseases.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 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
44 citing papers in PubMed, 59 citations in OpenAlex.
- Exploratory biomarker analysis in the phase III L-MOCA study of olaparib maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer.BMC medicine · 2024Trial
- Persistent interferon signaling and clonal expansion mark early events in DNA methylation damage-induced liver cancer.NAR cancer · 2026Article
- Th17 cells require the DNA repair sensor xeroderma pigmentosum complementation Group C to control oxidative DNA damage in a murine model.Nature communications · 2026Article
- A post-translational regulatory map of chronic antigen-driven human T cell dysfunction.bioRxiv : the preprint server for biology · 2026Article
- DNA Damage and Repair in Thyroid Physiology and Disease.Endocrine reviews · 2026Review
- Persistent interferon signaling and clonal expansion mark early events in DNA methylation damage-induced liver cancer.bioRxiv : the preprint server for biology · 2025Article
- Robust prediction of synthetic gRNA activity and cryptic DNA repair by disentangling cellular CRISPR cleavage outcomes.Nature communications · 2025Article
- Unveiling the Role of Selenium in Child Development: Impacts on Growth, Neurodevelopment and Immunity.Journal of clinical medicine · 2025Review
- Modification in Structures of Active Compounds in Anticancer Mitochondria-Targeted Therapy.International journal of molecular sciences · 2025Review
- DDIT3 deficiency ameliorates systemic lupus erythematosus by regulating B cell activation and differentiation.Life medicine · 2025Article
- Elucidating the immunomodulatory roles and mechanisms of CUL4B in the immune system: a comprehensive review.Frontiers in immunology · 2025Review
- Modulation of TCR stimulation and pifithrin-α improve the genomic safety profile of CRISPR-engineered human T cells.Cell reports. Medicine · 2024Article
- Crosstalk among WEE1 Kinase, AKT, and GSK3 in Nav1.2 Channelosome Regulation.International journal of molecular sciences · 2024Article
- Profiling Proteins and Phosphorylation Sites During T Cell Activation Using an Integrated Thermal Shift Assay.Molecular & cellular proteomics : MCP · 2024Article
- CRL4b Inhibition Ameliorates Experimental Autoimmune Encephalomyelitis Progression.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Comparison of protective effects of nicotinamide mononucleotide and nicotinamide riboside on DNA damage induced by cisplatin in HeLa cells.Biochemistry and biophysics reports · 2024Article
- The Proteasome Inhibitor Bortezomib Induces p53-Dependent Apoptosis in Activated B Cells.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Review
- Effects of SMC1A on immune microenvironment and cancer stem cells in colon adenocarcinoma.Cancer medicine · 2023Article
- Inflammation and DNA damage: cause, effect or both.Nature reviews. Rheumatology · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 6 institutions in 1 country.
Funding
Abstract
Antigen-activated lymphocytes undergo extraordinarily rapid cell division in the course of immune responses. We hypothesized that this unique aspect of lymphocyte biology leads to unusual genomic stress in recently antigen-activated lymphocytes and that targeted manipulation of DNA damage-response (DDR) signaling pathways would allow for selective therapeutic targeting of pathological T cells in disease contexts. Consistent with these hypotheses, we found that activated mouse and human T cells display a pronounced DDR in vitro and in vivo. Upon screening a variety of small-molecule compounds, we found that potentiation of p53 (via inhibition of MDM2) or impairment of cell cycle checkpoints (via inhibition of CHK1/2 or WEE1) led to the selective elimination of activated, pathological T cells in vivo. The combination of these strategies [which we termed "p53 potentiation with checkpoint abrogation" (PPCA)] displayed therapeutic benefits in preclinical disease models of hemophagocytic lymphohistiocytosis and multiple sclerosis, which are driven by foreign antigens or self-antigens, respectively. PPCA therapy targeted pathological T cells but did not compromise naive, regulatory, or quiescent memory T-cell pools, and had a modest nonimmune toxicity profile. Thus, PPCA is a therapeutic modality for selective, antigen-specific immune modulation with significant translational potential for diverse immune-mediated diseases.
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.