ArticleFrontiers in immunology2021
Activation of the DDR Pathway Leads to the Down-Regulation of the TGFβ Pathway and a Better Response to ICIs in Patients With Metastatic Urothelial Carcinoma.
Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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
30 citing papers in PubMed, 49 citations in OpenAlex.
- Temporal dynamics in cancer immunotherapy: the interplay between circadian rhythms, tumor microenvironment, and immune checkpoint blockade.Journal of the National Cancer Center · 2026Review
- Systematic Pathway Screening via Integrated Machine Learning Identifies FOXO-Mediated Transcription Signature for Robust Immunotherapy Response Prediction in Non-Small Cell Lung Cancer.Human mutation · 2026Article
- Insights from pharmacovigilance databases, clinical cohorts and preclinical models into VEGF(R) inhibitor-induced arthritis in cancer.Communications medicine · 2025Article
- The microbiome in cancer.iMeta · 2025Review
- Alterations and correlation between DNA damage and repair response and PD-L1 expression in non-small cell lung cancers.BMC cancer · 2025Article
- NK Cell Senescence in Cancer: From Molecular Mechanisms to Therapeutic Opportunities.Aging and disease · 2025Review
- Article
- Decoding the mechanisms behind second primary cancers.Journal of translational medicine · 2025Review
- Predictive value of ZFHX4 mutation for the efficacy of immune checkpoint inhibitors in non-small cell lung cancer and melanoma.Investigational new drugs · 2024Article
- Integration analysis using bioinformatics and experimental validation on cellular signalling for sex differences of hypertrophic cardiomyopathy.Journal of cellular and molecular medicine · 2024Article
- Toxicity profiles of immune checkpoint inhibitors in nervous system cancer: a comprehensive disproportionality analysis using FDA adverse event reporting system.Clinical and experimental medicine · 2024Article
- PESSA: A web tool for pathway enrichment score-based survival analysis in cancer.PLoS computational biology · 2024Article
- DNA damage response alterations in clear cell renal cell carcinoma: clinical, molecular, and prognostic implications.European journal of medical research · 2024Article
- Germline DNA damage response gene mutations as predictive biomarkers of immune checkpoint inhibitor efficacy.Frontiers in immunology · 2024Article
- Article
- Article
- Gamma delta T-cell-based immune checkpoint therapy: attractive candidate for antitumor treatment.Molecular cancer · 2023Review
- Advanced Acral Melanoma Therapies: Current Status and Future Directions.Current treatment options in oncology · 2022Review
- The role of DNA damage repair (DDR) system in response to immune checkpoint inhibitor (ICI) therapy.Journal of experimental & clinical cancer research : CR · 2022Review
- Icaritin inhibits PLK1 to activate DNA damage response in NK/T cell lymphoma and increases sensitivity to GELOX regime.Molecular therapy oncolytics · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immune checkpoint inhibitors (ICIs) have changed the treatment paradigm of metastatic urothelial carcinoma (mUC), a dominant type of bladder cancer (BC). Previous studies have shown an association between gene mutations in the DNA damage response (DDR) pathway and the immunotherapy response in mUC but have neglected the effect of the activation level of the DDR pathway on the ICI response in mUC. A published immunotherapy cohort with genome, transcriptome and survival data for 348 mUC patients was used. An external cohort (The Cancer Genome Atlas Bladder Cancer) and the GSE78220 cohort were used for validation. The activation level of the DDR pathway was quantified using single-sample gene set enrichment analysis (ssGSEA). Further analysis on the genome, immunogenicity, and the immune microenvironment was conducted using the DDR ssGSEA enrichment score-high (DSSH) group and the DDR ssGSEA enrichment score-low (DSSL) group. In the mUC cohorts, the DSSH group was associated with longer overall survival times (P=0.026; Hazard ratio=0.67; 95%CI: 0.46-0.95). The DSSH group was also associated with higher tumor mutation burden, neoantigen load, immune-activated cell patterns, and immune-related gene expression levels. The GSEA results indicated an immune activation state in DSSH group, which correlated with a down-regulation in the transforming growth factor β receptor signaling pathway. Our study suggests that the activation level of the DDR pathway may be a novel predictive marker for immunotherapy efficacy in patients with mUC.
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.