ArticleJournal of hematology & oncology2016
Targeting of PI3K/AKT/mTOR pathway to inhibit T cell activation and prevent graft-versus-host disease development.
Article in Journal of hematology & oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 117 citations in OpenAlex.
- Acute Graft-vs.-Host Disease-Associated Endothelial ActivationFrontiers in immunology · 2019Trial
- Superior GVHD-free, relapse-free survival for G-BM to G-PBSC grafts is associated with higher MDSCs content in allografting for patients with acute leukemia.Journal of hematology & oncology · 2017Trial
- The roles of ginseng and ginsenosides for immune regulation: Relation to immunometabolic responses.Journal of ginseng research · 2026Review
- Dynamic responses in the human methylome to exertional heat exhaustion, heat injury, and heat stroke.Human genomics · 2026Article
- Plant-Derived Compounds as Potential Sensitizers to Immunotherapy in Melanoma.International journal of molecular sciences · 2026Review
- Integrating Multi-Omics Atlas to Uncover Genetic and Epigenetic Mechanisms and Reveal Cell State Evolution Across Ecotypes in Male Urological Cancers.International journal of molecular sciences · 2026Article
- Nanomedicine in Organ Transplantation: From Graft Preservation and Repair to Immunomodulation and Monitoring.Theranostics · 2026Review
- A Spatiotemporal Model of CXCL10 as a Master Regulator of Immune Evasion and Metastasis in Osteosarcoma.International journal of molecular sciences · 2025Review
- Bypassing cisplatin resistance in Nrf2 hyperactivated head and neck cancer through effective PI3Kinase targeting.British journal of cancer · 2025Article
- Review
- Orlistat facilitates immunotherapy via AKT-FOXO3a-FOXM1-mediated PD-L1 suppression.Journal for immunotherapy of cancer · 2025Article
- Review
- Pan-cancer and multi-omics analysis: NDUFA1 is a potential therapeutic target and prognostic marker for esophageal cancer.Cell biology and toxicology · 2025Article
- CD155 promotes the progression of colorectal cancer by restraining CD8Cancer immunology, immunotherapy : CII · 2025Article
- Construction and verification of an innovative immune-related and hallmark gene sets prognostic model for bladder cancer.Translational cancer research · 2024Article
- PI3K/mTOR inhibition induces tumour microenvironment remodelling and sensitises pS6Clinical and translational medicine · 2024Article
- Association between Immune Checkpoint Inhibitors and Atherosclerotic Cardiovascular Disease Risk: Another Brick in the Wall.International journal of molecular sciences · 2024Review
- Galectin-9 alleviates acute graft-versus-host disease after haplo-hematopoietic stem cell transplantation by regulating regulatory T cell/effector T cell imbalance.Immunity, inflammation and disease · 2024Article
- Targeting the chemokines in acute graft-versus-host disease.Frontiers in immunology · 2024Review
- Rapamycin Augmentation of Chronic Ketamine as a Novel Treatment for Complex Regional Pain Syndrome.Cureus · 2023Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGraft-versus-host disease (GvHD) remains the major obstacle to successful allogeneic hematopoietic stem cell transplantation, despite of the immunosuppressive regimens administered to control T cell alloreactivity. PI3K/AKT/mTOR pathway is crucial in T cell activation and function and, therefore, represents an attractive therapeutic target to prevent GvHD development. Recently, numerous PI3K inhibitors have been developed for cancer therapy. However, few studies have explored their immunosuppressive effect.
methodsThe effects of a selective PI3K inhibitor (BKM120) and a dual PI3K/mTOR inhibitor (BEZ235) on human T cell proliferation, expression of activation-related molecules, and phosphorylation of PI3K/AKT/mTOR pathway proteins were analyzed. Besides, the ability of BEZ235 to prevent GvHD development in mice was evaluated.
resultsSimultaneous inhibition of PI3K and mTOR was efficient at lower concentrations than PI3K specific targeting. Importantly, BEZ235 prevented naïve T cell activation and induced tolerance of alloreactive T cells, while maintaining an adequate response against cytomegalovirus, more efficiently than BKM120. Finally, BEZ235 treatment significantly improved the survival and decreased the GvHD development in mice.
conclusionsThese results support the use of PI3K inhibitors to control T cell responses and show the potential utility of the dual PI3K/mTOR inhibitor BEZ235 in GvHD prophylaxis.
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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.