Evidence map›Paper›PMID 39929976›Full record

ArticleNature microbiology2025

Gut microbiota-derived hexa-acylated lipopolysaccharides enhance cancer immunotherapy responses.

Puspendu Sardar, Benjamin S Beresford-Jones, Wangmingyu Xia, Omar Shabana, Satoshi Suyama, Ruben J F Ramos, Amelia T Soderholm, Panagiotis Tourlomousis, Paula Kuo, Alexander C Evans and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature microbiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 1 pooled it
–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

23 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  10. Effects ofFrontiers in microbiology · 2026
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  12. Ferrum@albumin assembled nanoclusters inhibit NF-Acta pharmaceutica Sinica. B · 2025
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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

21 authors.

Puspendu Sardar *Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0001-8011-2915
Benjamin S Beresford-Jones *Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge, UK.
Wangmingyu Xia *Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge, UK.
Omar ShabanaCambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0002-1947-8018
Satoshi SuyamaCambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge, UK.
Ruben J F RamosDonald B. and Catherine C. Marron Cancer Metabolism Center, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-3350-0437
Amelia T SoderholmCambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge, UK.
Panagiotis TourlomousisCambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge, UK.
Paula KuoDepartment of Pathology, School of Biological Sciences, University of Cambridge, Cambridge, UK.
Alexander C EvansDepartment of Pathology, School of Biological Sciences, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0002-6363-2684
Charlotte J ImianowskiDepartment of Pathology, School of Biological Sciences, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0002-7116-7591
Alberto G ContiDepartment of Pathology, School of Biological Sciences, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0003-0725-337X
Alexander J WesolowskiDepartment of Pathology, School of Biological Sciences, University of Cambridge, Cambridge, UK.
Natalie M BakerCambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0009-0001-0586-2828
Emily A L McCordCambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge, UK.
Klaus OkkenhaugDepartment of Pathology, School of Biological Sciences, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0002-9432-4051
Sarah K WhitesideDepartment of Pathology, School of Biological Sciences, University of Cambridge, Cambridge, UK.
Rahul RoychoudhuriDepartment of Pathology, School of Biological Sciences, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0002-5392-1853
Clare E BryantCambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0002-2924-0038
Justin R CrossDonald B. and Catherine C. Marron Cancer Metabolism Center, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Virginia A PedicordCambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge, UK. vap33@cam.ac.uk.ORCID http://orcid.org/0000-0001-9625-3122

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020) EP/X024709/1NCI NIH HHS P30 CA008748Rosetrees Trust A2194Wellcome TrustWellcome Trust (Wellcome) 206245/Z/17/ZWellcome Trust (Wellcome) 302351/Z/23/Z
6 · The paper itself

Abstract

The gut microbiome modulates immunotherapy treatment responses, and this may explain why immune checkpoint inhibitors, such as anti-PD-1, are only effective in some patients. Previous studies correlated lipopolysaccharide (LPS)-producing gut microbes with poorer prognosis; however, LPS from diverse bacterial species can range from immunostimulatory to inhibitory. Here, by functionally analysing faecal metagenomes from 112 patients with melanoma, we found that a subset of LPS-producing bacteria encoding immunostimulatory hexa-acylated LPS was enriched in microbiomes of clinical responders. In an implanted tumour mouse model of anti-PD-1 treatment, microbiota-derived hexa-acylated LPS was required for effective anti-tumour immune responses, and LPS-binding antibiotics and a small-molecule TLR4 antagonist abolished anti-PD-1 efficacy. Conversely, oral administration of hexa-acylated LPS to mice significantly augmented anti-PD-1-mediated anti-tumour immunity. Penta-acylated LPS did not improve anti-PD-1 efficacy in vivo and inhibited hexa-acylated LPS-induced immune activation in vitro. Microbiome hexa-acylated LPS therefore represents an accessible predictor and potential enhancer of immunotherapy responses.

Indexed as

Gastrointestinal MicrobiomeImmunotherapyLipopolysaccharidesMelanomaAcylationAnimalsBacteriaCell Line, TumorFecesFemaleHumansImmune Checkpoint InhibitorsMaleMiceMice, Inbred C57BLProgrammed Cell Death 1 ReceptorImmune Checkpoint InhibitorsLipopolysaccharidesProgrammed Cell Death 1 ReceptorToll-Like Receptor 4

Identifiers

PMID39929976
PMCPMC11879847

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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.