ArticleNature medicine2021
Gut microbiota signatures are associated with toxicity to combined CTLA-4 and PD-1 blockade.
3 registry-linked trialsOpen access · greenAbstract read
In one paragraph
Article in Nature medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 300 papers, 4 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
300citing papers in PubMed, 4 pooled it
24.8field-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.
The Gut Microbiome and Sorafenib Maintenance Therapy in FMS-like Tyrosine Kinase 3 (FLT3)/Internal Tandem Duplication (ITD) Positive Acute Myeloid Leukemia (AML) Patients After Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT)
The Gut Microbiome Changes in FMS-like Tyrosine Kinase 3 (FLT3)-ITD Positive Acute Myeloid Leukemia Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation With or Without Sorafenib Maintenance Post-transplantation
The Gut Microbiome Changes in FMS-like Tyrosine Kinase 3 (FLT3) Negative Acute Leukemia (AL) Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT) With or Without Sorafenib Maintenance Post-transplantation
Who cites it
300 citing papers in PubMed, 4 syntheses or guidelines pooled it, 398 citations in OpenAlex.
- Research landscape, thematic evolution, and translational insights of immune checkpoint inhibitor-induced colitis: a bibliometric analysis (2006-2025).Frontiers in immunology · 2026Pooled it
- Functional convergence amid taxonomic variability in gut microbiome-immune checkpoint inhibitor research: a bibliometric and mechanistic synthesis.Frontiers in immunology · 2026Pooled it
- A gut microbial signature for combination immune checkpoint blockade across cancer types.Nature medicine · 2024Pooled it
- Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of melanoma, version 3.0.Journal for immunotherapy of cancer · 2023Guideline
- A prospective randomized controlled pilot study of gut microbiome modulation by Nigella sativa seed oil and thymoquinone metabolism in healthy volunteers: implications for gastrointestinal surgery.Scientific reports · 2026Trial
- Safety and efficacy of fecal microbiota transplantation in solid cancers resistant to immune checkpoint inhibitors: results of the MITRIC trial.Journal for immunotherapy of cancer · 2026Trial
- Gut microbiota diversity is prognostic and associated with benefit from chemo-immunotherapy in metastatic triple-negative breast cancer.Molecular oncology · 2025Trial
- Neoadjuvant vidutolimod and nivolumab in high-risk resectable melanoma: A prospective phase II trial.Cancer cell · 2024Trial
- Randomized Placebo-Controlled, Biomarker-Stratified Phase Ib Microbiome Modulation in Melanoma: Impact of Antibiotic Preconditioning on Microbiome and Immunity.Cancer discovery · 2024Trial
- Efficacy, safety, and biomarker analysis of nivolumab in combination with abemaciclib plus endocrine therapy in patients with HR-positive HER2-negative metastatic breast cancer: a phase II study (WJOG11418B NEWFLAME trial).Journal for immunotherapy of cancer · 2023Trial
- Killing cancer takes guts: lessons learned from the manipulation of gut microbiome and immunotherapy for the future of urothelial carcinoma.Oncoimmunology · 2026Review
- Decoding the microbiome: artificial intelligence-targeted gut microenvironment breakthroughs in personalized cancer therapy.Gut microbes · 2026Review
- Review
- Immune checkpoint blockade reshapes drug-associated toxicity: a pharmacovigilance atlas of drug-ICI interactions.medRxiv : the preprint server for health sciences · 2026Article
- BRIDGE-KO: auditable transfer learning with bridged knockoffs improves cross-cohort microbiome prediction of immunotherapy response.Briefings in bioinformatics · 2026Article
- Emotional distress and clinical response to neoadjuvant chemoimmunotherapy in resectable non-small-cell lung cancer: a protocol for the prospective observational NeoFUSE-Lung cohort study.Translational lung cancer research · 2026Article
- Review
- Gut microbiota modulation of systemic immunity and cancer immunotherapy: mechanisms, evidence, and therapeutic implications.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2026Review
- Integrated Spatial and Bulk Untargeted Metabolomics Characterize Location- and Histology-Associated Metabolic Heterogeneity in Colorectal Cancer.Journal of proteome research · 2026Article
- Tryptophan degradation by intestinal Bacteroides induces anti-tumor immunity and limits melanoma growth.Cell reports. Medicine · 2026Article
240 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
71 authors at 12 institutions in 5 countries.
Miles C Andrews *Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0003-1231-8641
Connie P M Duong *Gustave Roussy Cancer Campus (GRCC), Villejuif, France.ORCID http://orcid.org/0000-0002-9067-8557
Vancheswaran Gopalakrishnan *Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Valerio Iebba *Gustave Roussy Cancer Campus (GRCC), Villejuif, France.ORCID http://orcid.org/0000-0002-0716-306X
Wei-Shen Chen *Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Lisa Derosa *Gustave Roussy Cancer Campus (GRCC), Villejuif, France.ORCID http://orcid.org/0000-0003-0527-2964
Md Abdul Wadud KhanDepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Alexandria P CogdillGustave Roussy Cancer Campus (GRCC), Villejuif, France.
Michael G WhiteDepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0001-5022-5505
Matthew C WongDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Gladys FerrereGustave Roussy Cancer Campus (GRCC), Villejuif, France.
Aurélie FluckigerGustave Roussy Cancer Campus (GRCC), Villejuif, France.
Maria P RobertiGustave Roussy Cancer Campus (GRCC), Villejuif, France.ORCID http://orcid.org/0000-0001-5788-6840
Paule OpolonGustave Roussy Cancer Campus (GRCC), Villejuif, France.
Maryam Tidjani AlouGustave Roussy Cancer Campus (GRCC), Villejuif, France.
Satoru YonekuraGustave Roussy Cancer Campus (GRCC), Villejuif, France.ORCID http://orcid.org/0000-0003-4047-3016
Whijae RohDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-7395-9939
Christine N SpencerDepartment of Informatics, Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA.
Irina Fernandez CurbeloDepartment of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Luis VenceDepartment of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0003-3441-4095
Alexandre ReubenDepartment of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0003-4510-0382
Sarah JohnsonDepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Reetakshi AroraDepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Golnaz MoradDepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-9460-618X
Matthew LastrapesMD Anderson Cancer Center University of Texas Health Graduate School of Biomedical Sciences (GSBS), Houston, TX, USA.
Erez N BaruchDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Latasha LittleDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Curtis GumbsDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Zachary A CooperAstraZeneca, Gaithersburg, MD, USA.ORCID http://orcid.org/0000-0003-1059-0940
Peter A PrietoDepartment of Surgery, University of Rochester Medical Center, Rochester, NY, USA.
Khalida WaniDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Alexander J LazarDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-6395-4499
Michael T TetzlaffDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Courtney W HudgensDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0001-8312-7485
Margaret K CallahanDepartment of Informatics, Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-9087-0012
Matthew AdamowDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-7709-0126
Michael A PostowDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Charlotte E AriyanDepartment of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Pierre-Olivier GaudreauDepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Luigi NeziIstituto Europeo di Oncologia, Milan, Italy.ORCID http://orcid.org/0000-0002-4670-7656
Didier RaoultAix-Marseille Université, MEPHI, IRD, IHU Méditerranée Infection, Marseille, France.ORCID http://orcid.org/0000-0002-0633-5974
Catalin MihalcioiuDepartment of Medicine, Faculty of Medicine and Health Sciences, McGill University Health Centre, Montreal, Quebec, Canada.
Arielle ElkriefCedars Cancer Center, McGill University Health Centre, Montreal, Quebec, Canada.
Rossanna C PezoDivision of Medical Oncology, University of Toronto, Sunnybrook Odette Cancer Centre, Toronto, Ontario, Canada.
Lauren E HayduDepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Julie M SimonDepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Hussein A TawbiDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0003-1942-851X
Jennifer McQuadeDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-2393-2172
Patrick HwuDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Wen-Jen HwuDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Rodabe N AmariaDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0001-6876-278X
Elizabeth M BurtonDepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Scott E WoodmanDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Stephanie WatowichDepartment of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0003-1969-659X
Adi DiabDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Sapna P PatelDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Isabella C GlitzaDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Michael K WongDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Li ZhaoDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jianhua ZhangDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0001-5412-9860
Nadim J AjamiDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Joseph PetrosinoDepartment of Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
Robert R JenqDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Michael A DaviesDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-0977-0912
Jeffrey E GershenwaldDepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
P Andrew FutrealDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0001-8663-2671
Padmanee SharmaDepartment of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0003-4658-055X
James P AllisonDepartment of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Bertrand RoutyGustave Roussy Cancer Campus (GRCC), Villejuif, France.
Laurence ZitvogelGustave Roussy Cancer Campus (GRCC), Villejuif, France. laurence.zitvogel@gustaveroussy.fr.ORCID http://orcid.org/0000-0003-1596-0998
Jennifer A WargoDepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. jwargo@mdanderson.org.ORCID http://orcid.org/0000-0003-3438-7576
The University of Texas MD Anderson Cancer Center · USInserm · FRMemorial Sloan Kettering Cancer Center · USMcGill University Health Centre · CAAix-Marseille Université · FRAstraZeneca (United States) · USBaylor College of Medicine · USEuropean Institute of Oncology · ITInstitut Gustave Roussy · FRParker Institute for Cancer Immunotherapy · USSunnybrook Health Science Centre · CAUniversity of Rochester Medical Center · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4MTumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8MResearch Project 2 - Targeting Melanoma Tumor Survival and Apoptotic MachineryU54CA224070 · NCI · WISTAR INSTITUTE · PI Jessie Villanueva · 2017 to 2026
$13.9MTRAINING OF ACADEMIC SURGICAL ONCOLOGISTST32CA009599 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Ashley M Holder, Jennifer A. Wargo · 1988 to 2026
$13.2MThe University of Texas MD Anderson Cancer Center SPORE in MelanomaP50CA221703 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DAVIES, MICHAEL · 2019 to 2023
$10.3M(PQ10) Enhancing responses to immune checkpoint blockade in melanoma via modulation of the microbiomeR01CA219896 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI WARGO, JENNIFER A. · 2018 to 2022
$2.2MMultidisciplinary Subspecialty Pathology Research Fellowship ProgramT32CA163185 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI CZERNIAK, BOGDAN A, KEYOMARSI, KHANDAN · 2011 to 2015
$1.7MNCI NIH HHS P30 CA008748NCI NIH HHS P30 CA016672NCI NIH HHS P50 CA221703NCI NIH HHS R01 CA219896NCI NIH HHS T32 CA009599NCI NIH HHS T32 CA163185NCI NIH HHS U54 CA224070
Abstract
Treatment with combined immune checkpoint blockade (CICB) targeting CTLA-4 and PD-1 is associated with clinical benefit across tumor types, but also a high rate of immune-related adverse events. Insights into biomarkers and mechanisms of response and toxicity to CICB are needed. To address this, we profiled the blood, tumor and gut microbiome of 77 patients with advanced melanoma treated with CICB, with a high rate of any ≥grade 3 immune-related adverse events (49%) with parallel studies in pre-clinical models. Tumor-associated immune and genomic biomarkers of response to CICB were similar to those identified for ICB monotherapy, and toxicity from CICB was associated with a more diverse peripheral T-cell repertoire. Profiling of gut microbiota demonstrated a significantly higher abundance of Bacteroides intestinalis in patients with toxicity, with upregulation of mucosal IL-1β in patient samples of colitis and in pre-clinical models. Together, these data offer potential new therapeutic angles for targeting toxicity to CICB.
Indexed as
Gastrointestinal MicrobiomeAnimalsCell Line, TumorCTLA-4 AntigenFemaleHumansInterleukin-1betaMelanomaMiceMice, Inbred C57BLProgrammed Cell Death 1 ReceptorCTLA-4 AntigenCTLA4 protein, humanInterleukin-1betaPDCD1 protein, humanProgrammed Cell Death 1 Receptor
Identifiers
What OpenQuestion holds
Textmetadata
LicenceTDM
Read underepoch 390
Registered trials
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.