Evidence map›Paper›PMID 40849910›Full record

ArticleCell reports2025

A capsular polysaccharide from a healthy human microbiota member activates a Lag-3-NK cell axis to restrain colon cancer and augment immunotherapy.

Allison M Weis, Kaylyn M Bauer, William W Tang, Emmanuel Stephen-Victor, Rickesha Bell, D Garrett Brown, H Atakan Ekiz, Van Tran, Kendra A Klag, Eric A Swanson and 20 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

30 authors.

Allison M WeisDivision of Microbiology and Immunology, Department of Pathology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA.
Kaylyn M BauerDivision of Microbiology and Immunology, Department of Pathology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA.
William W TangDivision of Microbiology and Immunology, Department of Pathology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA.
Emmanuel Stephen-VictorDivision of Microbiology and Immunology, Department of Pathology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA.
Rickesha BellDivision of Microbiology and Immunology, Department of Pathology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA.
D Garrett BrownDivision of Microbiology and Immunology, Department of Pathology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA.
H Atakan EkizDepartment of Molecular Biology and Genetics, Izmir Institute of Technology, Gulbahce, Urla, Izmir 35430, Turkey.
Van TranDivision of Microbiology and Immunology, Department of Pathology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA.
Kendra A KlagDivision of Microbiology and Immunology, Department of Pathology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA.
Eric A SwansonDivision of Microbiology and Immunology, Department of Pathology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA; Department of Pathology, Scripps Clinic Medical Group, La Jolla, CA, USA.
Logan BarriosDivision of Microbiology and Immunology, Department of Pathology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA.
Morgan HarwoodDivision of Microbiology and Immunology, Department of Pathology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA.
Jennifer H HillDivision of Microbiology and Immunology, Department of Pathology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA.
Kyla S OstDivision of Microbiology and Immunology, Department of Pathology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA; University of Colorado Anschutz School of Medicine, Department of Immunology and Microbiology, Aurora, CO, USA.
Biljana GigicHeidelberg University Hospital, Department of General, Visceral and Transplantation Surgery, Heidelberg, Germany.
Martin SchneiderHeidelberg University Hospital, Department of General, Visceral and Transplantation Surgery, Heidelberg, Germany.
Jennifer OseDepartment of Population Health Science, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA.
Sheetal HardikarDepartment of Population Health Science, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA.
Adetunji T ToriolaDivision of Public Health Sciences, Department of Surgery, Siteman Cancer Center Washington University School of Medicine, St. Louis, MO, USA.
David ShibataDepartment of Surgery, University of Tennessee Health Science Center, Memphis, TN, USA.
Christopher I LiFred Hutchinson Cancer Center, University of Washington, Seattle, WA, USA.
Jane C FigueiredoDepartment of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Doratha A ByrdDepartment of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
Erin M SiegelDepartment of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
Kathleen ArnoldsUniversity of Colorado Anschutz School of Medicine, Department of Biomedical Informatics, Aurora, CO, USA.
Catherine LozuponeUniversity of Colorado Anschutz School of Medicine, Department of Biomedical Informatics, Aurora, CO, USA.
Cornelia M UlrichDepartment of Population Health Science, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA.
Ryan M O'ConnellDivision of Microbiology and Immunology, Department of Pathology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA.
W Zac StephensDivision of Microbiology and Immunology, Department of Pathology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA.
June L RoundDivision of Microbiology and Immunology, Department of Pathology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA. Electronic address: june.round@path.utah.edu.

Funding

Determining immune-mediated mechanisms of beneficial bacteria in colon cancerK22CA289144 · NCI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI ALLISON WEIS · 2025 to 2026
$404k
Determining how the human gut microbiota modulates colon cancer tumorigenesisF32CA243501 · NCI · UNIVERSITY OF UTAH · PI WEIS, ALLISON · 2019 to 2021
$200k
NCI NIH HHS F32 CA243501NCI NIH HHS K22 CA289144
6 · The paper itself

Abstract

Colorectal cancer (CRC) is increasing globally, making identification of preventative measures necessary. Transplantation of the microbiota from CRC and non-CRC patients into mice demonstrates that non-diseased individuals possess organisms that reduce tumor formation and highlights Bacteriodes uniformis as protective. B. uniformis is reduced in humans with CRC, and proactive treatment with B. uniformis slows tumor growth in mice. Natural killer (NK) cells, but not T cells, are required for B. uniformis-mediated protection. CRC is recalcitrant to immunotherapies; however, addition of B. uniformis restores response to α-CTLA-4 treatment in an NK cell-dependent manner. We report that high Lag-3 expression is associated with greater survival in CRC patients and that B. uniformis-mediated protection is reliant on Lag-3 in innate cells. Induction of NK cell activity and reduced tumor growth is dependent on a specific B. uniformis capsular polysaccharide. Thus, healthy individuals possess tumor suppressor microbes that prevent cancer development and can be harnessed therapeutically.

Indexed as

Antigens, CDColonic NeoplasmsImmunotherapyKiller Cells, NaturalMicrobiotaPolysaccharides, BacterialAnimalsFemaleGastrointestinal MicrobiomeHumansLymphocyte Activation Gene 3 ProteinMaleMiceMice, Inbred C57BLAntigens, CDLymphocyte Activation Gene 3 ProteinPolysaccharides, Bacterialcancercapsulescolon cancerCP: CancerCP: Microbiologyhuman samplesLag-3microbiologymicrobiomeNK cellstumor immunology

Identifiers

PMID40849910
PMCPMC13270923

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Registered trials

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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.