ArticleImmunity2022
Tryptophan-derived microbial metabolites activate the aryl hydrocarbon receptor in tumor-associated macrophages to suppress anti-tumor immunity.
Registry-linked trialOpen access · greenAbstract read
In one paragraph
Article in Immunity, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06272240 (Study of the Role of the Tumor Microenvironment in Ovarian Cancer), which is not on this map. Cited by 448 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
448citing papers in PubMed, 1 pooled it
49.6field-weighted citation impact, top 1% of its field
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.
Study of the Role of the Tumor Microenvironment in Ovarian Cancer
Who cites it
448 citing papers in PubMed, 1 synthesis or guideline pooled it, 644 citations in OpenAlex.
- The microbiome-nitric oxide axis in cancer immunotherapy: a targeted qualitative systematic review of mechanistic and translational evidence.Frontiers in immunology · 2026Pooled it
- Amino acid metabolic reprogramming by gut microbiota: a novel metabolic checkpoint in the tumor microenvironment.Gut microbes · 2026Review
- IntratumorGut microbes · 2026Article
- Multi-omics analysis of saccharomyces boulardii supplementation reveals coordinated microbiome, metabolic, and immune signaling changes accompanying tumor suppression.Gut microbes · 2026Article
- Isolation of Bacteria and Fungi from Human Pancreatic Tumors and Duodenum.Gut microbes · 2026Article
- Spatiotemporal dynamics of the host-tumor metabolic interface: Implications for precision nutritional oncology.Genes & diseases · 2026Review
- Targeting myeloid cell plasticity and metabolic reprogramming to alleviate T cell dysfunction and exhaustion-associated states and enhance immune checkpoint blockade therapy.Biomarker research · 2026Review
- Enteric ChAT-Expressing Neurons Mediate the Protective Effect of Lactobacillus plantarum in Inflammatory Bowel Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Trimethylamine-N-oxide: the microbial cue in immune-mediated disorders.Trends in endocrinology and metabolism: TEM · 2026Review
- Harnessing microfluidics for microbiology: from bacteria-host interactions to emerging cancer therapies.Communications biology · 2026Review
- Tissue-Resident Macrophages: Linking Physiology and Inflammation in Infection.Clinical reviews in allergy & immunology · 2026Review
- Molecular pathways linking the gut microbiome to antitumor immunity.Trends in microbiology · 2026Review
- SIX1 drives acute myeloid leukemia progression by reprogramming glycolytic metabolism and impairing CD8⁺ T-cell effector function.Immunologic research · 2026Article
- Chronic Stress Promotes Gastric Cancer Metastasis by Inducing Microbiota-Associated Kynurenine Accumulation and Macrophage Remodeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Lactiplantibacillus plantarum Mediated Tryptophan Metabolism to Alleviate Tropomyosin-induced Food Allergy.Probiotics and antimicrobial proteins · 2026Article
- Microbiota in pancreatic cancer: Roles in tumor initiation and progression (Review).Oncology letters · 2026Review
- Tryptophan metabolism in tumor microenvironment and therapeutic implications.Journal of advanced research · 2026Review
- Low-protein diet enhances antitumor immunity in pancreatic cancer through microbiota-derived UDP-galactose.Nature cancer · 2026Article
- The Metabolic Rheostat Index Uncovers Pathway-Level Coordination, Immunosuppressive Microenvironment Remodeling, and Therapeutic Co-Vulnerabilities in Pancreatic Ductal Adenocarcinoma.Current issues in molecular biology · 2026Article
- Gut microbiota modulation of gastrointestinal cancers: from dysbiosis signatures to therapeutic interventions.Acta pharmacologica Sinica · 2026Review
388 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
30 authors at 6 institutions in 3 countries.
Kebria HezavehTumor Immunotherapy Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada.
Rahul S ShindeTumor Immunotherapy Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada.
Andreas KlötgenDepartment of Computational Biology of Infection Research, Helmholtz Centre for Infection Research, Braunschweig 38124, Germany.
Marie Jo HalabyTumor Immunotherapy Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada.
Sara LamorteTumor Immunotherapy Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada.
M Teresa CiudadTumor Immunotherapy Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada.
Rene QuevedoTumor Immunotherapy Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada.
Luke NeufeldTumor Immunotherapy Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada; Department of Immunology, The University of Toronto, Toronto, ON M5S 1A8, Canada.
Zhe Qi LiuTumor Immunotherapy Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada; Department of Immunology, The University of Toronto, Toronto, ON M5S 1A8, Canada.
Robbie JinTumor Immunotherapy Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada; Department of Immunology, The University of Toronto, Toronto, ON M5S 1A8, Canada.
Barbara T GrünwaldPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
Elisabeth G FoersterDepartment of Immunology, The University of Toronto, Toronto, ON M5S 1A8, Canada.
Danica ChaharlangiDepartment of Molecular Genetics, The University of Toronto, Toronto, ON M5S 1A8, Canada.
Mengdi GuoTumor Immunotherapy Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada; Department of Immunology, The University of Toronto, Toronto, ON M5S 1A8, Canada.
Priya MakhijaniTumor Immunotherapy Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada; Department of Immunology, The University of Toronto, Toronto, ON M5S 1A8, Canada.
Xin ZhangTumor Immunotherapy Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada.
Trevor J PughTumor Immunotherapy Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada; Department of Medical Biophysics, The University of Toronto, Toronto, ON M5G 1L7, Canada; The Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.
Devanand M PintoNational Research Council, Human Health Therapeutics, Halifax, NS B3H 3Z1, Canada.
Ileana L CoInstitute of Biomedical Engineering, The University of Toronto, Toronto, ON M5S 3G9, Canada.
Alison P McGuiganInstitute of Biomedical Engineering, The University of Toronto, Toronto, ON M5S 3G9, Canada; Department of Chemical Engineering and Applied Chemistry, The University of Toronto, Toronto, ON M5S 3E5, Canada.
Gun Ho JangThe Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.
Rama KhokhaPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Medical Biophysics, The University of Toronto, Toronto, ON M5G 1L7, Canada.
Pamela S OhashiTumor Immunotherapy Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada; Department of Immunology, The University of Toronto, Toronto, ON M5S 1A8, Canada.
Grainne M O'KaneThe Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; Division of Medical Oncology, Department of Medicine, The University of Toronto, Toronto, ON M5S 3H2, Canada.
Steven GallingerThe Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; Department of Laboratory Medicine and Pathobiology, The University of Toronto, Toronto, ON M5S 1A8, Canada; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada.
William W NavarreDepartment of Molecular Genetics, The University of Toronto, Toronto, ON M5S 1A8, Canada.
Heather MaughanRonin Institute, Montclair, NJ 07043, USA.
Dana J PhilpottDepartment of Immunology, The University of Toronto, Toronto, ON M5S 1A8, Canada.
David G BrooksTumor Immunotherapy Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada; Department of Immunology, The University of Toronto, Toronto, ON M5S 1A8, Canada.
Tracy L McGahaTumor Immunotherapy Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada; Department of Immunology, The University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address: tmcgaha@uhnresearch.ca.
University Health Network · CAUniversity of Toronto · CAOntario Institute for Cancer Research · CAHelmholtz Centre for Infection Research · DENational Research Council Canada · CARonin Institute · US
Funding
Tumor Microenvironment and MetastasisP30CA010815 · NCI · WISTAR INSTITUTE · PI Luis J Montaner · 1985 to 2026
$75.9MMechanistic investigations of microbiome-driven aryl hydrocarbon receptor activity and macrophage function in pancreatic cancer.R01CA255670 · NCI · UNIVERSITY HEALTH NETWORK · PI MCGAHA, TRACY L · 2021 to 2025
$1.8MThe role of marginal zone macrophages and immuno-metabolism in tumor-driven MDSC developmentR01CA190449 · NCI · UNIVERSITY HEALTH NETWORK · PI MCGAHA, TRACY L · 2015 to 2020
$1.3MMechanistic relationships between IDO, GCN2, and mTOR signals in immunity to apoptotic cellsR01AR067763 · NIAMS · UNIVERSITY HEALTH NETWORK · PI MCGAHA, TRACY L · 2015 to 2019
$1.2MNCI NIH HHS P30 CA010815NCI NIH HHS R01 CA190449NCI NIH HHS R01 CA255670NIAMS NIH HHS R01 AR067763
Abstract
The aryl hydrocarbon receptor (AhR) is a sensor of products of tryptophan metabolism and a potent modulator of immunity. Here, we examined the impact of AhR in tumor-associated macrophage (TAM) function in pancreatic ductal adenocarcinoma (PDAC). TAMs exhibited high AhR activity and Ahr-deficient macrophages developed an inflammatory phenotype. Deletion of Ahr in myeloid cells or pharmacologic inhibition of AhR reduced PDAC growth, improved efficacy of immune checkpoint blockade, and increased intra-tumoral frequencies of IFNγ
Indexed as
AnimalsCarcinoma, Pancreatic DuctalCD8-Positive T-LymphocytesHumansImmune ToleranceIndolesLymphocytes, Tumor-InfiltratingMiceMicrobiotaPancreatic NeoplasmsPrognosisReceptors, Aryl HydrocarbonTryptophanTumor-Associated MacrophagesTumor MicroenvironmentIndolesReceptors, Aryl HydrocarbonTryptophanaryl hydrocarbon receptorimmune suppressionimmunotherapyindolesmacrophagemetabolismmicrobiomepancreatic cancerT cellstumor microenvironment
Identifiers
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Read underepoch 390
Registered trials
NCT06272240ClinicalTrials.gov
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.