ArticleOncotarget2016
Ceramide activates lysosomal cathepsin B and cathepsin D to attenuate autophagy and induces ER stress to suppress myeloid-derived suppressor cells.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 85 citations in OpenAlex.
- Therapeutic effect and autophagy regulation of myriocin in nonalcoholic steatohepatitis.Lipids in health and disease · 2019Trial
- CD200Nature communications · 2026Article
- Hepatic ceramide synthesis links systemic inflammation to organelle dysfunction in cancer.bioRxiv : the preprint server for biology · 2025Article
- Cathepsins: Emerging targets in the tumor ecosystem to overcome cancers.Seminars in cancer biology · 2025Review
- Autophagy in tumor immune escape and immunotherapy.Molecular cancer · 2025Review
- The Prediction Model for Triple-Negative Breast Cancer Prognosis and Immunotherapy Efficacy Based on Single-Cell Sequencing of CD8+ T cells.Journal of Cancer · 2025Article
- A Low Expression of NRF2 Enhances Oxidative Stress and Autophagy in Myofibroblasts, Promoting Progression of Chronic Obstructive Pulmonary Disease.Current medicinal chemistry · 2025Article
- Mitochondria-targeted strategies in tumor immunity.Frontiers in immunology · 2025Review
- Advances in ORMDL Research in Malignant Tumors: A Review.OncoTargets and therapy · 2025Review
- The multifaceted roles of cathepsins in immune and inflammatory responses: implications for cancer therapy, autoimmune diseases, and infectious diseases.Biomarker research · 2024Review
- Lysosomal dysfunction in α-synuclein pathology: molecular mechanisms and therapeutic strategies.Cellular and molecular life sciences : CMLS · 2024Review
- Podocyte-specific silencing of acid sphingomyelinase gene to abrogate hyperhomocysteinemia-induced NLRP3 inflammasome activation and glomerular inflammation.American journal of physiology. Renal physiology · 2024Article
- Fanning the Flames of Endoplasmic Reticulum (ER) Stress: Can Sphingolipid Metabolism Be Targeted to Enhance ER Stress-Associated Immunogenic Cell Death in Cancer?Molecular pharmacology · 2024Review
- The Role of Ceramide and Sphingolipid Metabolism in Cancer Therapeutics.Journal of oncology research and therapy · 2024Article
- Acid Ceramidase Inhibitor LCL-805 Antagonizes Akt Signaling and Promotes Iron-Dependent Cell Death in Acute Myeloid Leukemia.Cancers · 2023Article
- The crosstalk between autophagy and myeloid-derived suppressor cell responses in cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Review
- GBA1 Variants and Parkinson's Disease: Paving the Way for Targeted Therapy.Journal of movement disorders · 2023Article
- Nanosecond pulsed electric field ablation-induced modulation of sphingolipid metabolism is associated with Ly6c2Molecular oncology · 2023Article
- Article
- Cold Atmospheric Plasma Triggers Apoptosis via the Unfolded Protein Response in Melanoma Cells.Cancers · 2023Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Myeloid-derived suppressor cells (MDSCs) are immune suppressive cells that are hallmarks of human cancer. MDSCs inhibit cytotoxic T lymphocytes (CTLs) and NK cell functions to promote tumor immune escape and progression, and therefore are considered key targets in cancer immunotherapy. Recent studies determined a key role of the apoptosis pathways in tumor-induced MDSC homeostasis and it is known that ceramide plays a key role in regulation of mammalian cell apoptosis. In this study, we aimed to determine the efficacy and underlying molecular mechanism of ceramide in suppression of MDSCs. Treatment of tumor-bearing mice with LCL521, a lysosomotropic inhibitor of acid ceramidase, significantly decreased MDSC accumulation in vivo. Using a MDSC-like myeloid cell model, we determined that LCL521 targets lysosomes and increases total cellular C16 ceramide level. Although MDSC-like cells have functional apoptosis pathways, LCL521-induced MDSC death occurs in an apoptosis- and necroptosis-independent mechanism. LCL521 treatment resulted in an increase in the number of autophagic vesicles, heterolysosomes and swollen ERs. Finally, concomitant inhibition of cathepsin B and cathepsin D was required to significantly decrease LCL521-induced cell death. Our observations indicate that LCL521 targets lysosomes to activate cathepsin B and cathepsin D, resulting in interrupted autophagy and ER stress that culminates in MDSC death. Therefore, a ceramidase inhibitor is potentially an effective adjunct therapeutic agent for suppression of MDSCs to enhance the efficacy of CTL-based cancer immunotherapy.
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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.