ArticleJournal of translational medicine2023
ALOX5 acts as a key role in regulating the immune microenvironment in intrahepatic cholangiocarcinoma, recruiting tumor-associated macrophages through PI3K pathway.
Article in Journal of translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- Cholangiocarcinoma:Unveiling the cold tumor microenvironment and strategies for immune rejuvenation.Oncogene · 2026Review
- AI-guided CRISPR screening reveals therapeutic targets in psoriasis.Nature communications · 2026Article
- The Evolving Landscape of Immune Regulation and Immunotherapy in Cholangiocarcinoma and Biliary Tract Cancer.Cancers · 2026Review
- USP1-mediated lipophagy-lipogenesis axis drives cholangiocarcinoma progression and immune evasion.Journal for immunotherapy of cancer · 2026Article
- Irisin regulates lipid metabolism and ferroptosis in ovarian cancer cells by modulating the ALOX5-5-HETE-PD-L1 axis.Scientific reports · 2026Article
- Stratifying cholangiocarcinoma: tumor microenvironment, molecular drivers, and novel immunotherapeutic approaches.Clinical and molecular hepatology · 2026Review
- SLAMF8 Promotes M2 Polarization of Macrophages and Enhances Breast Cancer Proliferation.Breast cancer (Dove Medical Press) · 2026Article
- Transcriptional activation of ALOX5 by c-Myc drives malignant progression and M2 macrophage polarization in clear cell renal cell carcinoma.American journal of cancer research · 2026Article
- MTH1 in the disorders of the central nervous system: scope beyond brain tumors and challenges.Acta neurologica Belgica · 2025Review
- Identification of M2 macrophage-related biomarkers for a predictive model of interstitial fibrosis and tubular atrophy after kidney transplantation by machine learning algorithms.Translational andrology and urology · 2025Article
- EZH2 regulates tumor-associated macrophages by the KDM6A-mediated inflammatory response in HPV16-positive cervical cancer.Human cell · 2025Article
- Metabolic reprogramming in hepatocellular carcinoma: an integrated omics study of lipid pathways and their diagnostic potential.Journal of translational medicine · 2025Article
- Role of the USP family in autophagy regulation and cancer progression.Apoptosis : an international journal on programmed cell death · 2025Review
- Lipid Metabolism Reprogramming in Tumor-Associated Macrophages Modulates Their Function in Primary Liver Cancers.Cancers · 2025Review
- From "metabolic storm" to "immune paralysis": the dynamic evolution of macrophages and metabolism reprogramming in ARDS.Frontiers in immunology · 2025Review
- A Machine Learning Computational Framework Develops a Multiple Programmed Cell Death Index for Improving Clinical Outcomes in Bladder Cancer.Biochemical genetics · 2024Article
- Identification and validation of an immune-derived multiple programmed cell death index for predicting clinical outcomes, molecular subtyping, and drug sensitivity in lung adenocarcinoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Article
- Tumor-associated macrophages: orchestrators of cholangiocarcinoma progression.Frontiers in immunology · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundIntrahepatic cholangiocarcinoma (ICC) is poorly treated due to the presence of an inhibitory immune microenvironment. Tumor-associated macrophages (TAM) are an important component of TME. ALOX5 is an important lipid metabolism enzyme in cancer progression, but the mechanism by which it regulates TAM to promote ICC progression is unknown. The aim of this study was to investigate the potential mechanism of TAM regulation by ALOX5 and the translational effect of targeting ALOX5.
methodsIn this study, we investigated the association between the spatial localization of epithelial cells and TAMs by combining scRNA-seq analysis with multiplex immunofluorescence analysis. Through bulk sequencing analysis and spatial analysis, lipid metabolism genes closely related to TAM infiltration were screened. In vitro co-culture model was constructed to verify that ALOX5 and its downstream metabolite LTB4 promote M2 macrophage migration. Bulk sequencing after co-culture combined with single-cell analysis was performed to identify key pathways for up-regulation of M2 macrophage migration. Finally, the effect of CSF1R inhibitor (PLX3397) combined with ALOX5 inhibitor (Zileuton) in vivo was investigated by by xenograft tumor formation experiment in nude mice.
resultsALOX5 in ICC cells was a key lipid metabolism gene affecting the infiltration of M2 macrophages in TME. Mechanically, LTB4, a metabolite downstream of ALOX5, recruited M2 macrophages to migrate around tumor cells by binding to BLT1/BLT2 and activating the PI3K pathway, which ultimately lead to the promotion of ICC progression. Targeting CSF1R in combination with ALOX5 inhibitor effectively reduced tumor volume and M2 macrophage infiltration abundance.
conclusionIn ICC, LTB4, a metabolite secreted by ALOX5 of epithelial cells, binded to BLT1/BLT2 on TAM surface to activate PI3K pathway and promote TAM migration, thus promoting ICC progression. Targeting CSF1R in combination with ALOX5 inhibitor for ICC is a promising combination therapy modality.
Indexed as
Identifiers
What OpenQuestion holds
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.