ArticleJournal of immunology (Baltimore, Md. : 1950)2016
Deletion of 5-Lipoxygenase in the Tumor Microenvironment Promotes Lung Cancer Progression and Metastasis through Regulating T Cell Recruitment.
Article in Journal of immunology (Baltimore, Md. : 1950), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 77 citations in OpenAlex.
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- Inflammation and gut barrier function-related genes and colorectal cancer risk in western European populations.Mutagenesis · 2025Article
- Metabolic gatekeepers: harnessing tumor-derived metabolites to optimize T cell-based immunotherapy efficacy in the tumor microenvironment.Cell death & disease · 2024Review
- Neutrophils in the premetastatic niche: key functions and therapeutic directions.Molecular cancer · 2024Review
- The frequency and function of nucleoprotein-specific CD8Journal of virology · 2024Article
- The deregulation of arachidonic acid metabolism in ovarian cancer.Frontiers in oncology · 2024Review
- Novel EGFR-mutant mouse models of lung adenocarcinoma reveal adaptive immunity requirement for durable osimertinib response.Cancer letters · 2023Article
- Metabonomic analysis of tumor microenvironments: a mini-review.Frontiers in oncology · 2023Review
- Mast cell-mediated immune regulation in health and disease.Frontiers in medicine · 2023Review
- RASAL3 predicts overall survival and CD8+ T lymphocyte infiltration in lung adenocarcinoma.Journal of cellular and molecular medicine · 2022Article
- STING suppresses bone cancer pain via immune and neuronal modulation.Nature communications · 2021Article
- Article
- Survival-Critical Genes Associated with Copy Number Alterations in Lung Adenocarcinoma.Cancers · 2021Article
- miR-18a promotes glioblastoma development by down-regulating ALOXE3-mediated ferroptotic and anti-migration activities.Oncogenesis · 2021Article
- Recent Metabolomics Analysis in Tumor Metabolism Reprogramming.Frontiers in molecular biosciences · 2021Review
- Lipid Metabolism in Tumor-Associated Macrophages.Advances in experimental medicine and biology · 2021Review
- Communication between human macrophages and epithelial cancer cell lines dictates lipid mediator biosynthesis.Cellular and molecular life sciences : CMLS · 2020Article
- Aberrant lipid metabolism in hepatocellular carcinoma cells as well as immune microenvironment: A review.Cell proliferation · 2020Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Eicosanoids, including PGs, produced by cyclooxygenases (COX), and leukotrienes, produced by 5-lipoxygenase (5-LO) have been implicated in cancer progression. These molecules are produced by both cancer cells and the tumor microenvironment (TME). We previously reported that both COX and 5-LO metabolites increase during progression in an orthotopic immunocompetent model of lung cancer. Although PGs in the TME have been well studied, less is known regarding 5-LO products produced by the TME. We examined the role of 5-LO in the TME using a model in which Lewis lung carcinoma cells are directly implanted into the lungs of syngeneic WT mice or mice globally deficient in 5-LO (5-LO-KO). Unexpectedly, primary tumor volume and liver metastases were increased in 5-LO-KO mice. This was associated with an ablation of leukotriene (LT) production, consistent with production mainly mediated by the microenvironment. Increased tumor progression was partially reproduced in global LTC4 synthase KO or mice transplanted with LTA4 hydrolase-deficient bone marrow. Tumor-bearing lungs of 5-LO-KO had decreased numbers of CD4 and CD8 T cells compared with WT controls, as well as fewer dendritic cells. This was associated with lower levels of CCL20 and CXL9, which have been implicated in dendritic and T cell recruitment. Depletion of CD8 cells increased tumor growth and eliminated the differences between WT and 5-LO mice. These data reveal an antitumorigenic role for 5-LO products in the microenvironment during lung cancer progression through regulation of T cells and suggest that caution should be used in targeting this pathway in lung cancer.
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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.