Evidence map›Paper›PMID 35217892›Full record

ArticleCancer immunology, immunotherapy : CII2022

Murine fecal microbiota transfer models selectively colonize human microbes and reveal transcriptional programs associated with response to neoadjuvant checkpoint inhibitors.

Fyza Y Shaikh, Joell J Gills, Fuad Mohammad, James R White, Courtney M Stevens, Hua Ding, Juan Fu, Ada Tam, Richard L Blosser, Jada C Domingue and 10 more

Open access · greenAbstract read
In one paragraph

Article in Cancer immunology, immunotherapy : CII, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 1 pooled it
2.7field-weighted citation impact, top 8% 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

22 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.

  1. Pooled it
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  8. Article
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  13. Fecal microbial transplants as investigative tools in cancer.American journal of physiology. Gastrointestinal and liver physiology · 2024
    Review
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  20. Gut microbiota in colorectal cancer development and therapy.Nature reviews. Clinical oncology · 2023
    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

20 authors at 5 institutions in 3 countries.

Fyza Y ShaikhThe Bloomberg-Kimmel Institute of Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Joell J GillsThe Bloomberg-Kimmel Institute of Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Fuad MohammadThe Bloomberg-Kimmel Institute of Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
James R WhiteResphera Biosciences, Baltimore, MD, USA.
Courtney M StevensThe Bloomberg-Kimmel Institute of Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Hua DingDepartment of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Baltimore, MD, USA.
Juan FuThe Bloomberg-Kimmel Institute of Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Ada TamThe Bloomberg-Kimmel Institute of Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Richard L BlosserThe Bloomberg-Kimmel Institute of Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jada C DomingueThe Bloomberg-Kimmel Institute of Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Tatianna C LarmanDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jamie E ChaftDepartment of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medicine, New York, NY, USA.
Jonathan D SpicerDepartment of Surgery, Division of Thoracic Surgery, Faculty of Medicine, Goodman Cancer Research Center, McGill University, Montreal, Canada.
Joshua E ReussDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jarushka NaidooThe Bloomberg-Kimmel Institute of Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Patrick M FordeThe Bloomberg-Kimmel Institute of Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Sudipto GangulyThe Bloomberg-Kimmel Institute of Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Franck HousseauThe Bloomberg-Kimmel Institute of Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Drew M PardollThe Bloomberg-Kimmel Institute of Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Cynthia L SearsThe Bloomberg-Kimmel Institute of Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA. csears@jhmi.edu.ORCID http://orcid.org/0000-0003-4059-1661
Bloomberg (United States) · USJohns Hopkins University · USMcGill University · CAMemorial Sloan Kettering Cancer Center · USResphera Biosciences · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI Rosalie Wollett · 1985 to 2026
$208.6M
ONCOLOGY: CHEMOTHERAPY, IMMUNOLOGY, BIOLOGYT32CA009071 · NCI · JOHNS HOPKINS UNIVERSITY · PI Mary Y Armanios, Nilofer S. Azad · 1985 to 2026
$12.8M
Institute for Clinical and Translational ResearchKL2TR001077 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$9.2M
Metabolite driven mechanisms by which gut microbes impact checkpoint inhibitor success in non-small cell lung cancer patientsK08CA263316 · NCI · JOHNS HOPKINS UNIVERSITY · PI SHAIKH, FYZA Y · 2021 to 2025
$1.1M
NCATS NIH HHS KL2 TR001077NCATS NIH HHS KL2TR001077NCI NIH HHS K08 CA263316NCI NIH HHS P30 CA006973NCI NIH HHS P30 CA008748NCI NIH HHS T32 CA009071NIH HHS P30 CA006973NIH HHS T32CA009071
6 · The paper itself

Abstract

Human gut microbial species found to associate with clinical responses to immune checkpoint inhibitors (ICIs) are often tested in mice using fecal microbiota transfer (FMT), wherein tumor responses in recipient mice may recapitulate human responses to ICI treatment. However, many FMT studies have reported only limited methodological description, details of murine cohorts, and statistical methods. To investigate the reproducibility and robustness of gut microbial species that impact ICI responses, we performed human to germ-free mouse FMT using fecal samples from patients with non-small cell lung cancer who had a pathological response or nonresponse after neoadjuvant ICI treatment. R-FMT mice yielded greater anti-tumor responses in combination with anti-PD-L1 treatment compared to NR-FMT, although the magnitude varied depending on mouse cell line, sex, and individual experiment. Detailed investigation of post-FMT mouse microbiota using 16S rRNA amplicon sequencing, with models to classify and correct for biological variables, revealed a shared presence of the most highly abundant taxa between the human inocula and mice, though low abundance human taxa colonized mice more variably after FMT. Multiple Clostridium species also correlated with tumor outcome in individual anti-PD-L1-treated R-FMT mice. RNAseq analysis revealed differential expression of T and NK cell-related pathways in responding tumors, irrespective of FMT source, with enrichment of these cell types confirmed by immunohistochemistry. This study identifies several human gut microbial species that may play a role in clinical responses to ICIs and suggests attention to biological variables is needed to improve reproducibility and limit variability across experimental murine cohorts.

Indexed as

Carcinoma, Non-Small-Cell LungLung NeoplasmsAnimalsFecal Microbiota TransplantationHumansMiceNeoadjuvant TherapyReproducibility of ResultsRNA, Ribosomal, 16SRNA, Ribosomal, 16SBiological variablesFecal microbiota transferGut microbiomeImmune checkpoint inhibitorsLung cancerNeoadjuvant

Identifiers

PMID35217892
PMCPMC9411268
OpenAlexW4214496408

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.