ArticleCancer letters2018
Inhibiting Notch1 enhances immunotherapy efficacy in melanoma by preventing Notch1 dependent immune suppressive properties.
Article in Cancer letters, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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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
25 citing papers in PubMed, 45 citations in OpenAlex.
- TYRP1 defines a proliferative melanoma cell subpopulation, driving malignant progression and therapy resistance via the GPNMB-Notch1-SOX10/MITF axis.Journal of translational medicine · 2026Article
- A longitudinal, multi-omic atlas reveals the emergence of a spatially organized immunosuppressive ecosystem in resistant melanoma.Cell reports. Medicine · 2026Article
- Targeting the Notch1-YY1-ICAM1 Signaling Axis Enhances the Efficacy of Immunotherapy in HCC by Activating CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A qualitative prognostic biomarker for melanoma based on the relative methylation orderings of CpG loci.Epigenetics · 2025Article
- Co-inhibition of Notch1 and ChK1 triggers genomic instability and melanoma cell death increasing the lifespan of mice bearing melanoma brain metastasis.Journal of experimental & clinical cancer research : CR · 2025Article
- Targeting Neuronal Nitric Oxide Synthase (nNOS) as a Novel Approach to Enhancing the Anti-Melanoma Activity of Immune Checkpoint Inhibitors.Pharmaceutics · 2025Article
- Notch1 blockade by a novel, selective anti-Notch1 neutralizing antibody improves immunotherapy efficacy in melanoma by promoting an inflamed TME.Journal of experimental & clinical cancer research : CR · 2024Article
- Personalized Immunotherapy Achieves Complete Response in Metastatic Adenoid Cystic Carcinoma Despite Lack of Conventional Biomarkers.Current oncology (Toronto, Ont.) · 2024Article
- Cannabinoid combination targetseLife · 2024Article
- Nivolumab and Ipilimumab Acting as Tormentors of Advanced Tumors by Unleashing Immune Cells and Associated Collateral Damage.Pharmaceutics · 2024Review
- Programmed death receptor ligand-2 (PD-L2) bearing extracellular vesicles as a new biomarker to identify early triple-negative breast cancer patients at high risk for relapse.Journal of cancer research and clinical oncology · 2023Article
- Oncogenic signaling pathway mediated by Notch pathway-related genes induces immunosuppression and immunotherapy resistance in hepatocellular carcinoma.Immunogenetics · 2022Article
- Identifying key mutations of radioresponsive genes in esophageal squamous cell carcinoma.Frontiers in immunology · 2022Article
- Pharmacological modulation of myeloid-derived suppressor cells to dampen inflammation.Frontiers in immunology · 2022Review
- Cryoablation reshapes the immune microenvironment in the distal tumor and enhances the anti-tumor immunity.Frontiers in immunology · 2022Article
- Distinct mutational backgrounds and clonal architectures implicated prognostic discrepancies in small-cell carcinomas of the esophagus and lung.Cell death & disease · 2021Article
- Clinicopathological and molecular characteristics of patients with hypermutant lung cancer: A retrospective cohort study.Oncology letters · 2021Article
- PLK1 and NOTCH Positively Correlate in Melanoma and Their Combined Inhibition Results in Synergistic Modulations of Key Melanoma Pathways.Molecular cancer therapeutics · 2021Article
- Somatic mutations in genes associated with mismatch repair predict survival in patients with metastatic cancer receiving immune checkpoint inhibitors.Oncology letters · 2020Article
- NOTCH3 signaling is essential for NF-κB activation in TLR-activated macrophages.Scientific reports · 2020Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
We have previously shown that Notch1 plays a critical role in modulating melanoma tumor cell growth and survival. Here we show that Notch1 also contributes to an immune-suppressive tumor microenvironment (TME). Notch1 inhibition reduces immune suppressive cells (i.e. MDSCs and Tregs) while allowing the recruitment of functional CD8(+) T cells, leading to a decrease in the Tregs/CD8(+) ratio, a key parameter in assessing positive responses to immune-checkpoint inhibitors. Inhibition of Notch1 improves the antitumor activity of nivolumab and ipilimumab, particularly when given in combination. Mechanistically, tumor-associated Notch1 regulates the expression of several chemokines involved in MDSCs and Tregs recruitment. Among them, CCL5, IL6 and IL8, or MIP2 in mouse, were consistently reduced by Notch1 depletion in several human and mouse melanoma cell lines. Notch1 controls the transcription of IL8 and IL6; and the secretion of CCL5 likely by inhibiting the expression of SNAP23, a member of the SNAREs family of proteins involved in cell exocytosis. Inhibition of SNAP23 decreases CCL5 secretion similarly to Notch1 inhibition. Hence, targeting Notch1 would affect both melanoma intrinsic growth/survival properties, and provide an immune-responsive TME, thus improving immune therapy efficacy.
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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.