ArticleThe Journal of clinical investigation2023
Lysosomal lipid peroxidation regulates tumor immunity.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 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.
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
39 citing papers in PubMed, 52 citations in OpenAlex.
- The role of lysosome-dependent cell death in cancer.Apoptosis : an international journal on programmed cell death · 2026Review
- EPHA2/CD44-directed trafficking enhances endosomal leakiness and antisense therapy delivery.The Journal of cell biology · 2026Article
- Subcellular regulation of ferroptosis: roles of individual intracellular organelles and cross talk.American journal of physiology. Cell physiology · 2026Review
- [Prognostic value of palmitoyl-protein thioesterase-1 in gastric cancer and its regulatory role in tumor cell lipid metabolism].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- Targeting lysosome-dependent cell death in cancer: towards therapeutic strategies.Biomarker research · 2026Review
- Effects of environmental enrichment on lymph node mitochondrial-redox status and immune response in adult male C57BL/6 mice.Scientific reports · 2026Article
- Regulated cell death: a multidimensional regulatory network in the pathogenesis of renal fibrosis.Apoptosis : an international journal on programmed cell death · 2026Review
- RHBDL2 drives lipid metabolic reprogramming in osteosarcoma via USP3-mediated deubiquitination of PPT1.Cell death & disease · 2026Article
- Wogonin derivative V8 enhances bortezomib efficacy in gastric carcinoma by disrupting lysosome-mediated drug resistance.World journal of gastroenterology · 2026Article
- cGAS-IFN-I responses by extracting nuclear DNA from dying cells via nucleocytosis.Nature communications · 2026Article
- Spatiotemporal control of immunogenic cell death: rewiring tumor-immune dialogues for next-generation immunotherapy.Frontiers in immunology · 2026Review
- Targeting lung cancer: synergistic therapeutic strategy of cuproptosis and immunogenic cell death.Frontiers in cell and developmental biology · 2026Review
- Bridging metabolic reprogramming and targeted therapy: the critical role of S-palmitoylation in cancer.Frontiers in cell and developmental biology · 2026Review
- Disruption of cholesterol homeostasis by antidepressants induces immunogenic cell death.Oncoimmunology · 2025Article
- Glutaminase-1 Mediated Glutaminolysis to Glutathione Synthesis Maintains Redox Homeostasis and Modulates Ferroptosis Sensitivity in Cancer Cells.Cell proliferation · 2025Article
- Palmitoylation modulates antitumor immunity.Molecular biology reports · 2025Review
- PPT1 is a negative regulator of STING signaling in cancer cells and its inhibition reactivates immune surveillance in cold tumors.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- Lipid overload meets S-palmitoylation: a metabolic signalling nexus driving cardiovascular and heart disease.Cell communication and signaling : CCS · 2025Review
- From mitochondrial dysregulation to ferroptosis: Exploring new strategies and challenges in radioimmunotherapy (Review).International journal of oncology · 2025Review
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
Abstract
Lysosomal inhibition elicited by palmitoyl-protein thioesterase 1 (PPT1) inhibitors such as DC661 can produce cell death, but the mechanism for this is not completely understood. Programmed cell death pathways (autophagy, apoptosis, necroptosis, ferroptosis, and pyroptosis) were not required to achieve the cytotoxic effect of DC661. Inhibition of cathepsins, or iron or calcium chelation, did not rescue DC661-induced cytotoxicity. PPT1 inhibition induced lysosomal lipid peroxidation (LLP), which led to lysosomal membrane permeabilization and cell death that could be reversed by the antioxidant N-acetylcysteine (NAC) but not by other lipid peroxidation antioxidants. The lysosomal cysteine transporter MFSD12 was required for intralysosomal transport of NAC and rescue of LLP. PPT1 inhibition produced cell-intrinsic immunogenicity with surface expression of calreticulin that could only be reversed with NAC. DC661-treated cells primed naive T cells and enhanced T cell-mediated toxicity. Mice vaccinated with DC661-treated cells engendered adaptive immunity and tumor rejection in "immune hot" tumors but not in "immune cold" tumors. These findings demonstrate that LLP drives lysosomal cell death, a unique immunogenic form of cell death, pointing the way to rational combinations of immunotherapy and lysosomal inhibition that can be tested in clinical trials.
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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.