ArticleThe Journal of clinical investigation2025
Gut microbial metabolite 4-hydroxybenzeneacetic acid drives colorectal cancer progression via accumulation of immunosuppressive PMN-MDSCs.
Article in The Journal of clinical investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 32 papers.
What it found
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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
32 citing papers in PubMed.
- Trial
- Modulating the gut microbiota to enhance immune checkpoint inhibitor efficacy in colorectal cancer: mechanisms, therapeutic strategies, and clinical perspectives.Gut microbes · 2026Review
- Review
- Therapeutic Potential of Polysaccharide-Modulated Gut Microbiota-Immune Axis in Gastrointestinal Cancers: Modern Insights From Traditional Pharmacy.Molecular nutrition & food research · 2026Review
- Regulation of PD-1PD-L1 Immune Checkpoints by Gut Microbiota Metabolites and Their Clinical Translational Research: A Review.Immunity, inflammation and disease · 2026Review
- Artificial intelligence-based models for colorectal cancer diagnosis using laboratory tests: an exploratory retrospective case-control study.Translational cancer research · 2026Article
- Harnessing the gut microbiome for improved immune checkpoint inhibition in colorectal cancer immunotherapy: a narrative Review.Clinical and experimental medicine · 2026Review
- Mannose-binding lectin 2 secreted by hepatocellular carcinoma cells recruits and activates natural killer cells to reshape an immune-activated microenvironment.PLoS biology · 2026Article
- Targeting SLC5A2 suppresses colorectal tumour development by enhancing NK cell activity through extracellular vesicle-dependent MICA/B signalling.Clinical and translational medicine · 2026Article
- Targeting the gut microbiota-metabolite-immune axis in cancer immunotherapy: mechanistic interplay, therapeutic strategies, and translational applications-a narrative review.Translational cancer research · 2026Review
- Colorectal cancer pathogenesis, oncogenic signaling networks and targeted therapeutic advances.Molecular biomedicine · 2026Review
- Butyrate-producing Eubacterium rectale inhibits gastric carcinogenesis and augments the efficacy of immunotherapy.Journal of translational medicine · 2026Article
- The Gut-Brain-Immune Axis in Glioma: Emerging Mechanisms and Therapeutic Opportunities.Cellular and molecular neurobiology · 2026Review
- EREG promotes colorectal cancer progression and immune suppressive microenvironment formation through IL-17A/NF-κB pathway.Discover oncology · 2026Article
- Gut microbiota drives cancer evolution and therapy resistance.Molecular cancer · 2026Review
- MOF-Ag Nanozyme forInternational journal of nanomedicine · 2026Article
- Metabolite-driven protein modifications in immune signaling: from established principles to emerging pyruvylation.Frontiers in immunology · 2026Review
- Gut microbial metabolites in colorectal cancer: dual roles in tumorigenesis, immune crosstalk, and therapeutic innovation.Frontiers in cellular and infection microbiology · 2026Review
- Gut metabolites: key factors in the cross-talk between the gut microbiota and tumor immunotherapy.Frontiers in immunology · 2026Review
- Article
Corrections and comments
- Erratum issued
Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Colorectal cancer (CRC) is characterized by an immune-suppressive microenvironment that contributes to tumor progression and immunotherapy resistance. The gut microbiome produces diverse metabolites that feature unique mechanisms of interaction with host targets, yet the role of many metabolites in CRC remains poorly understood. In this study, the microbial metabolite 4-hydroxybenzeneacetic acid (4-HPA) promoted the infiltration of PMN myeloid-derived suppressor cells (PMN-MDSCs) in the tumor microenvironment, consequently inhibiting the antitumor response of CD8+ T cells and promoting CRC progression in vivo. Mechanistically, 4-HPA activates the JAK2/STAT3 pathway, which upregulates CXCL3 transcription, thereby recruiting PMN-MDSCs to the CRC microenvironment. Selective knockdown of CXCL3 resensitized tumors to anti-PD-1 immunotherapy in vivo. Chlorogenic acid reduces the production of 4-HPA by microbiota, likewise abolishing 4-HPA-mediated immunosuppression. The 4-HPA content in CRC tissues was notably increased in patients with advanced CRC. Overall, the gut microbiome uses 4-HPA as a messenger to control chemokine-dependent accumulation of PMN-MDSC cells and regulate antitumor immunity in CRC. Our findings provide a scientific basis for establishing clinical intervention strategies to reverse the tumor immune microenvironment and improve the efficacy of immunotherapy by reducing the interaction among intestinal microbiota, tumor cells, and tumor immune cells.
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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.