ArticleJournal of cancer science & therapy2018
Blocking PD1/PDL1 Interactions Together with MLN4924 Therapy is a Potential Strategy for Glioma Treatment.
Article in Journal of cancer science & therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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.
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Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
- Dual biomarker role of PD-L1 and LC3B in glioblastoma: prognostic and therapeutic potential.Neurosurgical review · 2026Review
- Mathematical model of tumor immune microenvironment with application to the combined therapy targeting the PD-1/PD-L1 pathway and IL-10 cytokine antibody.Theory in biosciences = Theorie in den Biowissenschaften · 2025Article
- The Double-Edged Effects of MLN4924: Rethinking Anti-Cancer Drugs Targeting the Neddylation Pathway.Biomolecules · 2024Review
- Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024Review
- Neddylation of protein, a new strategy of protein post-translational modification for targeted treatment of central nervous system diseases.Frontiers in neuroscience · 2024Review
- Article
- Pharmacologic targeting of Nedd8-activating enzyme reinvigorates T-cell responses in lymphoid neoplasia.Leukemia · 2023Article
- Targeting cullin neddylation for cancer and fibrotic diseases.Theranostics · 2023Review
- PD-L1 induction via the MEK-JNK-AP1 axis by a neddylation inhibitor promotes cancer-associated immunosuppression.Cell death & disease · 2022Article
- PD1/PD-L1 immune checkpoint as a potential target for preventing brain tumor progression.Cancer immunology, immunotherapy : CII · 2022Review
- A 1p/19q Codeletion-Associated Immune Signature for Predicting Lower Grade Glioma Prognosis.Cellular and molecular neurobiology · 2022Article
- FCGR3A Is a Prognostic Biomarker and Correlated with Immune Infiltrates in Lower-Grade Glioma.Journal of oncology · 2022Article
- Neddylation and anti-tumor immunity.Oncotarget · 2021Article
- Targeting the HuR Oncogenic Role with a New Class of Cytoplasmic Dimerization Inhibitors.Cancer research · 2021Article
- The Combination Therapy of Fluorouracil and Oxaliplatin Suppress the Progression of Colon Cancer Through miR-183-5p/SOCS3 Axis and Downregulating PD-L1.Cancer management and research · 2021Article
- The pivotal roles of neddylation pathway in immunoregulation.Immunity, inflammation and disease · 2020Review
- CD19-targeting fusion protein combined with PD1 antibody enhances anti-tumor immunity in mouse models.Oncoimmunology · 2020Article
- Validation of NEDD8-conjugating enzyme UBC12 as a new therapeutic target in lung cancer.EBioMedicine · 2019Article
- Glioblastoma vulnerability to neddylation inhibition is dependent on PTEN status, and dysregulation of the cell cycle and DNA replication.Neuro-oncology advancesArticle
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
objectiveMLN4924, a pharmacological inhibitor of cullin neddylation, resulted in glioma cell apoptosis, deregulation of the S-phase of DNA synthesis and thus, offers great potential for the treatment of brain tumours. However, targeting the neddylation pathway with an MLN4924 treatment stabilized the hypoxia-inducible factor 1A (HIF1A), which is one of the main transcriptional enhancers of the immune checkpoint molecule PDL1 (programmid death ligand-1) in cancer cells. The influence of immune checkpoint molecules on glioma progression has recently been discovered; PDL1 overexpression in gliomas corresponds to a significant shortening of patient survival and a decrease of the anti-tumour immune response. We hypothesize that i) PDL1 is up-regulated in gliomas after treatment with MLN4924 and induces T-cell energy; ii) co-utilization of the PD1/PDL1 blockage with MLN4924 therapy may reduce T-cell energy and may engage MLN4924-induced tumour disruption with the immune response.
methodsPDL1 expression and its immunosuppressive role in gliomas, glioma microenvironments, and after treatments with MLN4924 were assessed by utilizing methods of immunohistochemistry, molecular biology, and biochemistry.
resultsWe confirmed PDL1 overexpression in clinical brain tumour samples, PDGx and established glioma cell lines, extracellular media from glioma cells, and CSF (cerebrospinal fluid) samples from tumour-bearing mice. Our primary T-cell based assays verified that the up-regulation of PDL1 in tumour cells protects gliomas from T-cell treatment and reduces T-cell activation. We found that a pharmacological inhibitor of cullin neddylation, MLN4924, exhibited strong cytotoxicity towards PDGx and established glioma cell lines,
conclusionWe conclude that i) PDL1 up-regulation in gliomas and the glioma microenvironment is an important chemotherapeutic target; ii) MLN4924 therapy, combined with a blockage of the PD1/PDL1 pathway, should be considered as a potential strategy for glioma treatment.
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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.