ArticleCell2023
Dietary tryptophan metabolite released by intratumoral Lactobacillus reuteri facilitates immune checkpoint inhibitor treatment.
Open access · bronzeAbstract read
In one paragraph
Article in Cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 428 papers.
0numbers the graph read from it
0cells of the map it votes in
428citing papers in PubMed
58.3field-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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
428 citing papers in PubMed, 591 citations in OpenAlex.
- Trial
- Tumor ecosystem and microbiome features associated with efficacy and resistance to avelumab plus chemoradiotherapy in head and neck cancer.Nature cancer · 2026Trial
- IntratumorGut microbes · 2026Article
- Gut microbiota translocation and dissemination in health: can it be beneficial and purposeful?Gut microbes · 2026Review
- Article
- The role of gut microbes in production of aromatic carboxaldehydes.Gut microbes · 2026Article
- Microbiota as a modulator of drug response: targeting microbial-drug crosstalk in cancer therapy.Gut microbes · 2026Review
- The impact of gut microbiota and metabolite-driven immune cell spatiotemporal dynamics on tumors.Gut microbes · 2026Review
- Article
- Gut microbiota-derived metabolites as context-dependent modulators of Nrf2 signaling in inflammation-driven carcinogenesis.Gut microbes · 2026Review
- Indole-3-carboxaldehyde fromGut microbes · 2026Article
- Gut microbiota-driven IL-17A production by hepatic γδ T cells enhances neutrophil defense against systemicVirulence · 2026Article
- Spatiotemporal dynamics of the host-tumor metabolic interface: Implications for precision nutritional oncology.Genes & diseases · 2026Review
- Metabolic immune checkpoints (MICs) in cancer: from molecular mechanisms to challenges and opportunities in clinical translation.Signal transduction and targeted therapy · 2026Review
- Review
- Gut Microbial Topology and Metabolic Signatures Associated With Colorectal Neoplasia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Harnessing microfluidics for microbiology: from bacteria-host interactions to emerging cancer therapies.Communications biology · 2026Review
- Molecular pathways linking the gut microbiome to antitumor immunity.Trends in microbiology · 2026Review
- Mint3 suppresses cuproptosis by modulating the AHR signalling pathway to facilitate the progression of hepatocellular carcinoma.Science China. Life sciences · 2026Article
- Chronic Stress Promotes Gastric Cancer Metastasis by Inducing Microbiota-Associated Kynurenine Accumulation and Macrophage Remodeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
368 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
Authors and funding
25 authors at 6 institutions in 1 country.
Mackenzie J BenderDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Alex C McPhersonDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Infectious Diseases and Microbiology, University of Pittsburgh School of Public Health, Pittsburgh, PA, USA.
Catherine M PhelpsDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Graduate Program of Microbiology and Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Surya P PandeyDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Colin R LaughlinDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Jake H ShapiraDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Luzmariel Medina SanchezDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Graduate Program of Microbiology and Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Mohit RanaDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Tanner G RichieDivision of Biology, Kansas State University, Manhattan, KS, USA.
Tahliyah S MimsDepartment of Nutritional Sciences, University of Wisconsin-Madison, Madison, WI, USA.
Angela M Gocher-DemskeDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Luisa Cervantes-BarraganDepartment of Microbiology and Immunology, Emory University, Atlanta, GA, USA.
Steven J MullettDepartment of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Health Sciences Mass Spectrometry Core, University of Pittsburgh, Pittsburgh, PA, USA.
Stacy L GelhausDepartment of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Health Sciences Mass Spectrometry Core, University of Pittsburgh, Pittsburgh, PA, USA.
Tullia C BrunoDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA, USA; Cancer Immunology and Immunotherapy Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Nikki CannonGenetics and Microbiome Core, Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
John A McCullochGenetics and Microbiome Core, Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Dario A A VignaliDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA, USA; Cancer Immunology and Immunotherapy Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Reinhard HinterleitnerDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Cancer Immunology and Immunotherapy Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Alok V JoglekarDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Cancer Immunology and Immunotherapy Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA; Center for Systems Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Joseph F PierreDepartment of Nutritional Sciences, University of Wisconsin-Madison, Madison, WI, USA.
Sonny T M LeeDivision of Biology, Kansas State University, Manhattan, KS, USA.
Diwakar DavarCancer Immunology and Immunotherapy Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA; Department of Medicine and UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA.
Hassane M ZarourDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Cancer Immunology and Immunotherapy Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA; Department of Medicine and UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA.
Marlies MeiselDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Cancer Immunology and Immunotherapy Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA. Electronic address: marlies@pitt.edu.
University of Pittsburgh · USKansas State University · USNational Cancer Institute · USUniversity of Wisconsin–Madison · USEmory University · USUPMC Hillman Cancer Center · US
Funding
VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI JOHN C. BYRD · 1988 to 2026
$158.0MMentoring CoreP20GM103418 · NIGMS · UNIVERSITY OF KANSAS MEDICAL CENTER · PI Douglas E Wright · 2012 to 2026
$63.0MSynergies among inhibitory receptors in tolerance, cancer & antiviral immunityP01AI108545 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Dario AA Vignali · 2015 to 2026
$30.8MProject 5: Microenvironment manipulation using anti-angiogenics to improve immunotherapy in melanomaP50CA254865 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DELGOFFE, GREG M., KIRKWOOD, JOHN MUNN · 2021 to 2025
$10.4MTraining in Cellular & Molecular Mechanisms of Tumor RejectionT32CA082084 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Robert J Binder, Dario AA Vignali · 1999 to 2026
$9.2MAutoimmunity and Immunopathology Training ProgramT32AI089443 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SHLOMCHIK, MARK J · 2010 to 2024
$6.6MDetermining the contribution of microbial-derived metabolites to protective immunity in obesity-driven cancer risk.U01CA272541 · NCI · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI Liza Makowski-Hayes, Joseph F PIERRE · 2022 to 2026
$5.1MRole of microbial-modulated bile acid receptor signaling in breast cancerR01CA253329 · NCI · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI Katherine Loree Cook, Liza Makowski-Hayes · 2020 to 2026
$3.0MFecal Microbiota Transplant and PD-1 blockade in MelanomaR01CA222203 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI ZAROUR, HASSANE M · 2018 to 2022
$2.5MRole of dietary fiber-microbiota Interactions in the development and function of small intestinal T cellsR01DK129950 · NIDDK · EMORY UNIVERSITY · PI CERVANTES BARRAGAN, LUISA · 2021 to 2025
$2.4MTherapy with fecal microbiota transplantation and immune checkpoint blockade for solid tumorsU01CA268806 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI HASSANE M ZAROUR · 2022 to 2026
$2.4MSystemic immunoregulatory consequences of bacterial translocation during health and diseaseR01DK130897 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MEISEL, MARLIES · 2021 to 2025
$2.2MNCI NIH HHS F32 CA247004NCI NIH HHS P30 CA047904NCI NIH HHS P50 CA254865NCI NIH HHS R01 CA203689NCI NIH HHS R01 CA222203NCI NIH HHS R01 CA253329NCI NIH HHS R21 CA259636NCI NIH HHS T32 CA082084NCI NIH HHS U01 CA268806NCI NIH HHS U01 CA272541NIAID NIH HHS P01 AI108545NIAID NIH HHS R21 AI163721NIAID NIH HHS R56 AI168478NIAID NIH HHS T32 AI089443NIDDK NIH HHS R01 DK129950NIDDK NIH HHS R01 DK130897NIGMS NIH HHS P20 GM103418NIH HHS S10 OD023402
Abstract
The use of probiotics by cancer patients is increasing, including among those undergoing immune checkpoint inhibitor (ICI) treatment. Here, we elucidate a critical microbial-host crosstalk between probiotic-released aryl hydrocarbon receptor (AhR) agonist indole-3-aldehyde (I3A) and CD8 T cells within the tumor microenvironment that potently enhances antitumor immunity and facilitates ICI in preclinical melanoma. Our study reveals that probiotic Lactobacillus reuteri (Lr) translocates to, colonizes, and persists within melanoma, where via its released dietary tryptophan catabolite I3A, it locally promotes interferon-γ-producing CD8 T cells, thereby bolstering ICI. Moreover, Lr-secreted I3A was both necessary and sufficient to drive antitumor immunity, and loss of AhR signaling within CD8 T cells abrogated Lr's antitumor effects. Further, a tryptophan-enriched diet potentiated both Lr- and ICI-induced antitumor immunity, dependent on CD8 T cell AhR signaling. Finally, we provide evidence for a potential role of I3A in promoting ICI efficacy and survival in advanced melanoma patients.
Indexed as
Limosilactobacillus reuteriMelanomaTumor MicroenvironmentCD8-Positive T-LymphocytesDietHumansImmune Checkpoint InhibitorsReceptors, Aryl HydrocarbonTryptophanImmune Checkpoint InhibitorsReceptors, Aryl HydrocarbonTryptophanaryl hydrocarbon receptorimmune checkpoint inhibitorindole-3-aldehydeLactobacillus reuterimelanomamicrobial AhR ligandsmicrobial-host crosstalktryptophantumor microbiome
Identifiers
What OpenQuestion holds
Textmetadata
LicenceTDM
Read underepoch 390
Registered trials
None linked
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.