ArticleNature medicine2022
Gut microbiome correlates of response and toxicity following anti-CD19 CAR T cell therapy.
Erratum issuedOpen access · greenAbstract readMulticenter Study
In one paragraph
Article in Nature medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 221 papers, 6 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
221citing papers in PubMed, 6 pooled it
28.8field-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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
221 citing papers in PubMed, 6 syntheses or guidelines pooled it, 294 citations in OpenAlex.
- Central nervous system infections caused by carbapenem-resistant klebsiella pneumoniae after CAR T-cell therapy in a patient with preexisting colonization: a case report and literature review.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026Pooled it
- The gut microbiota-brain-CAR T cell axis: a systematic review of gut microbiome modulation and its impact on neurological complications and treatment responses in CAR T cell therapy.Frontiers in immunology · 2025Pooled it
- Best Practice Considerations by The American Society of Transplant and Cellular Therapy: Infection Prevention and Management After Chimeric Antigen Receptor T Cell Therapy for Hematological Malignancies.Transplantation and cellular therapy · 2024Guideline
- A systematic review and meta-analysis of nonrelapse mortality after CAR T cell therapy.Nature medicine · 2024Pooled it
- Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy.Nature reviews. Clinical oncology · 2023Pooled it
- A systematic review and meta-analysis evaluating the impact of antibiotic use on the clinical outcomes of cancer patients treated with immune checkpoint inhibitors.Frontiers in oncology · 2023Pooled it
- Trial
- A retrospectively registered pilot randomized controlled trial of postbiotic administration during antibiotic treatment increases microbiome diversity and enriches health-associated taxa.Infection and immunity · 2026Trial
- Gut microbiome modulates the outcome in primary central nervous system lymphoma patients undergoing chemotherapy: An ancillary study from the BLOCAGE trial.Neuro-oncology · 2025Trial
- Enhancing outcomes in medically inoperable early-stage NSCLC with gut-targeted antibiotics and stereotactic body radiotherapy: results from a randomized pilot study.Journal for immunotherapy of cancer · 2025Trial
- Trial
- 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
- The role of gut microbiome in aging-associated diseases: where do we stand now and how technology will transform the future.Gut microbes · 2026Review
- Review Article: Immune Effector Cell-Mediated Enterocolitis Following CAR-T Cell Therapy-Clinical Features, Pathophysiology and Management.Alimentary pharmacology & therapeutics · 2026Review
- Observational
- CAR-T Cell Therapy and Gut Microbiota Modulation in Multiple Sclerosis: Emerging Therapeutic Strategies and Current Limitations.Current issues in molecular biology · 2026Review
- Changes in C-Reactive Protein Forecast Infection Risk Following Treatment with Chimeric Antigen Receptor T Cells.Cancers · 2026Article
- Microbial Signals in Cancer: Dissecting Host-Microbiota-Tumor Interactions and Potential Therapeutic Strategy.MedComm · 2026Review
- Inclusion of Multi-Omic Biomarkers Improves Prediction Accuracy of Response, Relapse, and Overall Survival in Acute Myeloid Leukemia Patients Receiving High-Intensity Induction Chemotherapy.Cancer medicine · 2026Article
- The evolving role of cytokines for CAR-T cell manufacturing and beyond.Nature biomedical engineering · 2026Review
161 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
49 authors at 9 institutions in 2 countries.
Melody SmithAdult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-2702-0381
Anqi Dai *Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Guido Ghilardi *Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.
Kimberly V AmelsbergCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.
Sean M DevlinDepartment of Biostatistics and Epidemiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Raymone PajarilloCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.
John B SlingerlandAdult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Silvia BeghiDepartment of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
Pamela S HerreraAdult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Paul GiardinaAdult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Annelie ClurmanAdult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Emmanuel DwomohAdult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Gabriel ArmijoAdult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Antonio L C GomesAdult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0003-3790-3724
Eric R LittmannThe Duchossois Family Institute, University of Chicago, Chicago, IL, USA.
Jonas SchluterInstitute for Computational Medicine, New York University Langone Health, New York, NY, USA.ORCID http://orcid.org/0000-0002-6214-9367
Emily FontanaMolecular Microbiology Core Facility, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Ying TaurInfectious Disease Service, Department of Medicine, and Immunology Program, Sloan Kettering Institute, New York, NY, USA.ORCID http://orcid.org/0000-0002-6601-8284
Jae H ParkDepartment of Medicine, Weill Cornell Medical College, New York, NY, USA.ORCID http://orcid.org/0000-0002-2903-5130
Maria Lia PalombaDepartment of Medicine, Weill Cornell Medical College, New York, NY, USA.ORCID http://orcid.org/0000-0001-5099-9156
Elizabeth HaltonCellular Therapeutics Center, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Josel RuizAdult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Tania JainDivision of Hematologic Malignancies and Bone Marrow Transplantation, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.ORCID http://orcid.org/0000-0001-6854-773X
Martina PennisiDepartment of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
Aishat Olaide AfuyeAdult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-5751-3283
Miguel-Angel PeralesAdult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-5910-4571
Craig W FreyerDepartment of Pharmacy, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-6526-8134
Alfred GarfallCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.
Shannon GierCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.
Sunita NastaCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.
Daniel LandsburgCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.
James GersonCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.
Jakub SvobodaCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.
Justin CrossThe Donald B. and Catherine C. Marron Cancer Metabolism Center, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Elise A ChongCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-8895-1625
Sergio GiraltAdult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Saar I GillCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.
Isabelle RiviereCellular Therapeutics Center, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
David L PorterCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.
Stephen J SchusterCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.
Michel SadelainCenter for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-9031-8025
Noelle FreyCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.
Renier J BrentjensDepartment of Medicine, Weill Cornell Medical College, New York, NY, USA.ORCID http://orcid.org/0000-0002-3364-5388
Carl H JuneCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-0241-3557
Eric G PamerThe Duchossois Family Institute, University of Chicago, Chicago, IL, USA.
Jonathan U PeledAdult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-4029-7625
Andrea Facciabene *Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA. facciabe@pennmedicine.upenn.edu.ORCID http://orcid.org/0000-0002-9563-297X
Marcel R M van den Brink *Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. vandenbm@mskcc.org.ORCID http://orcid.org/0000-0003-0696-4401
Marco Ruella *Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA. mruella@upenn.edu.ORCID http://orcid.org/0000-0003-4301-5811
Memorial Sloan Kettering Cancer Center · USHospital of the University of Pennsylvania · USUPMC Hillman Cancer Center · USUniversity of Pennsylvania · USUniversity of Chicago · USJohns Hopkins University · USKettering University · USNYU Langone Health · USUniversity of Milan · IT
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4MT LYMPHOCYTE SUBSET FUNCTION POST-TRANSPLANTATIONP01CA023766 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI PAMER, ERIC G. · 1985 to 2023
$59.0MProject 3: Combinatorial and gene-editing approaches to enhance the efficacy of CAR T cell therapy of multiple myeloma.P01CA214278 · NCI · UNIVERSITY OF PENNSYLVANIA · PI CARL H. JUNE · 2017 to 2026
$26.8MThymic and Peripheral Aspects of T Cell Aging and RejuvenationP01AG052359 · NIA · UNIVERSITY OF ARIZONA · PI Lauren Ilyse Richie EHRLICH · 2017 to 2026
$23.5MThe role of intestinal microbiota in graft-versus-host diseaseR01CA228308 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI Philip L Lorenzi, Marcel R M van den Brink · 2018 to 2026
$5.2MThe role of autophagy gene Atg16L1 in allogeneic hematopoietic stem cell transplantation - Resubmission - 1R01HL123340 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI CADWELL, KEN HASHIGIWA, VAN DEN BRINK, MARCEL R M · 2015 to 2022
$5.2MRegulation of the intestinal stem cell compartment after hematopoietic transplantationR01HL125571 · NHLBI · SLOAN-KETTERING INST CAN RESEARCH · PI Alan M Hanash · 2015 to 2026
$4.4MThird-party “off the shelf” mature or precursor CAR T cells to prevent or treat malignant relapse after allo HCTR01HL147584 · NHLBI · SLOAN-KETTERING INST CAN RESEARCH · PI VAN DEN BRINK, MARCEL R M · 2019 to 2022
$2.7MThe role of intestinal microbiota in graft-versus-host diseaseR01CA228358 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI VAN DEN BRINK, MARCEL R M · 2018 to 2022
$2.6MMODULATION OF CD5 SIGNALING TO ENHANCE ADOPTIVE T-CELL THERAPIES FOR CANCERR37CA262362 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Marco Ruella · 2022 to 2026
$2.6M(PQ10) The impact of the gut microbiome on the anti-tumor effects of radiotherapyR01CA219871 · NCI · UNIVERSITY OF PENNSYLVANIA · PI FACCIABENE, ANDREA, KOUMENIS, CONSTANTINOS · 2018 to 2022
$2.4MDirecting the metabolic fate of CAR T cellsR01CA226983 · NCI · UNIVERSITY OF PENNSYLVANIA · PI JUNE, CARL H. · 2018 to 2022
$2.1MNCI NIH HHS K08 CA194256NCI NIH HHS K99 CA212302NCI NIH HHS P01 CA023766NCI NIH HHS P01 CA214278NCI NIH HHS P30 CA008748NCI NIH HHS R00 CA212302NCI NIH HHS R01 CA206012NCI NIH HHS R01 CA219871NCI NIH HHS R01 CA226983NCI NIH HHS R01 CA228308NCI NIH HHS R01 CA228358NHLBI NIH HHS K08 HL143189NHLBI NIH HHS R01 HL123340NHLBI NIH HHS R01 HL125571NHLBI NIH HHS R01 HL147584NIA NIH HHS P01 AG052359
Abstract
Anti-CD19 chimeric antigen receptor (CAR) T cell therapy has led to unprecedented responses in patients with high-risk hematologic malignancies. However, up to 60% of patients still experience disease relapse and up to 80% of patients experience CAR-mediated toxicities, such as cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. We investigated the role of the intestinal microbiome on these outcomes in a multicenter study of patients with B cell lymphoma and leukemia. We found in a retrospective cohort (n = 228) that exposure to antibiotics, in particular piperacillin/tazobactam, meropenem and imipenem/cilastatin (P-I-M), in the 4 weeks before therapy was associated with worse survival and increased neurotoxicity. In stool samples from a prospective cohort of CAR T cell recipients (n = 48), the fecal microbiome was altered at baseline compared to healthy controls. Stool sample profiling by 16S ribosomal RNA and metagenomic shotgun sequencing revealed that clinical outcomes were associated with differences in specific bacterial taxa and metabolic pathways. Through both untargeted and hypothesis-driven analysis of 16S sequencing data, we identified species within the class Clostridia that were associated with day 100 complete response. We concluded that changes in the intestinal microbiome are associated with clinical outcomes after anti-CD19 CAR T cell therapy in patients with B cell malignancies.
Indexed as
Gastrointestinal MicrobiomeNeurotoxicity SyndromesReceptors, Chimeric AntigenAntigens, CD19HumansImmunotherapy, AdoptiveProspective StudiesRetrospective StudiesAntigens, CD19Receptors, Chimeric Antigen
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