Evidence map›Paper›PMID 33758825›Full record

ArticleNeuro-oncology advances

Human gut microbial communities dictate efficacy of anti-PD-1 therapy in a humanized microbiome mouse model of glioma.

Kory J Dees, Hyunmin Koo, J Fraser Humphreys, Joseph A Hakim, David K Crossman, Michael R Crowley, L Burton Nabors, Etty N Benveniste, Casey D Morrow, Braden C McFarland

Open access · goldAbstract read
In one paragraph

Article in Neuro-oncology advances. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed, 1 pooled it
1.8field-weighted citation impact, top 15% of its field
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

37 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.

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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

10 authors at 1 institution in 1 country.

Kory J DeesDepartment of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Hyunmin KooDepartment of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
J Fraser HumphreysDepartment of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Joseph A HakimSchool of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
David K CrossmanDepartment of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Michael R CrowleyDepartment of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
L Burton NaborsDepartment of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Etty N BenvenisteDepartment of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Casey D MorrowDepartment of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Braden C McFarlandDepartment of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA.ORCID https://orcid.org/0000-0002-7517-9688
University of Alabama at Birmingham · US

Funding

XRAY CRYSTALLOGRAPHYP30CA013148 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Robert S Welner · 1985 to 2026
$165.9M
The Role of CK2 in Glioblastoma DevelopmentR01CA194414 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI BENVENISTE, ETTY N · 2016 to 2020
$1.7M
Using a Humanized Microbiome Mouse Model to Assess Therapeutic Response in GlioblastomaR03NS116559 · NINDS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI MCFARLAND, BRADEN COX · 2020 to 2021
$149k
NCI NIH HHS P30 CA013148NCI NIH HHS R01 CA194414NINDS NIH HHS R03 NS116559
6 · The paper itself

Abstract

backgroundAlthough immunotherapy works well in glioblastoma (GBM) preclinical mouse models, the therapy has not demonstrated efficacy in humans. To address this anomaly, we developed a novel humanized microbiome (HuM) model to study the response to immunotherapy in a preclinical mouse model of GBM.

methodsWe used 5 healthy human donors for fecal transplantation of gnotobiotic mice. After the transplanted microbiomes stabilized, the mice were bred to generate 5 independent humanized mouse lines (HuM1-HuM5).

resultsAnalysis of shotgun metagenomic sequencing data from fecal samples revealed a unique microbiome with significant differences in diversity and microbial composition among HuM1-HuM5 lines. All HuM mouse lines were susceptible to GBM transplantation, and exhibited similar median survival ranging from 19 to 26 days. Interestingly, we found that HuM lines responded differently to the immune checkpoint inhibitor anti-PD-1. Specifically, we demonstrate that HuM1, HuM4, and HuM5 mice are nonresponders to anti-PD-1, while HuM2 and HuM3 mice are responsive to anti-PD-1 and displayed significantly increased survival compared to isotype controls. Bray-Curtis cluster analysis of the 5 HuM gut microbial communities revealed that responders HuM2 and HuM3 were closely related, and detailed taxonomic comparison analysis revealed that

conclusionsThe results of our study establish the utility of humanized microbiome mice as avatars to delineate features of the host interaction with gut microbial communities needed for effective immunotherapy against GBM.

Indexed as

anti-PD-1GL261glioblastomaimmunotherapymicrobiome

Identifiers

PMID33758825
PMCPMC7967908
OpenAlexW3126186226

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.