ArticleThe Journal of experimental medicine2023
Intestinal toxicity to CTLA-4 blockade driven by IL-6 and myeloid infiltration.
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Article in The Journal of experimental medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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46citing papers in PubMed, 1 pooled it
5.7field-weighted citation impact, top 3% of its field
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 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
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- When Checkpoint Inhibitors Break Barriers: Mechanisms and Challenges of irAEs of the Skin, Gastrointestinal Tract, and Lung.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Review
- Risk factors and outcomes for steroid-refractory immune-related hepatotoxicity in locally advanced and metastatic cancer.Cancer immunology, immunotherapy : CII · 2026Article
- Targeting LRBA triggers CTLA4 degradation and antitumor immunity for cancer immunotherapy.Nature communications · 2025Article
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- Single-cell multiomics reveals macrophage-derived IL-23 and CXCL9/10 drive pathogenic IFNGJournal for immunotherapy of cancer · 2025Article
- Neutrophil extracellular traps-STC1 positive feedback loop promotes immune evasion and metastasis in bladder cancer.Journal for immunotherapy of cancer · 2025Article
- Precision Delivery of Active Compounds from Edible and Medicinal Plants via Gut Microbiota Targeting: A New Paradigm for Cancer Immunotherapy.Nutrients · 2025Review
- Secretory IgA amplification during immune checkpoint blockade enhances the control of tumor growth by enterotropic T cells.Science advances · 2025Article
- Navigating Cardiotoxicity in Immune Checkpoint Inhibitors: From Diagnosis to Long-Term Management.Journal of cardiovascular development and disease · 2025Review
- Roles of the gut microbiota in immune-related adverse events: mechanisms and therapeutic intervention.Nature reviews. Clinical oncology · 2025Review
- Smooth Muscle Silent Information Regulator 1 Contributes to Colitis in Mice.International journal of molecular sciences · 2025Article
- Baseline colitogenicity and acute perturbations of gut microbiota in immunotherapy-related colitis.The Journal of experimental medicine · 2025Article
- Breakthroughs in immune checkpoint therapy: overcoming NSCLC immune checkpoint therapy resistance with novel techniques.Frontiers in immunology · 2025Review
- Low rather than high interleukin-6 levels are associated with immune-related adverse events in cancer patients treated with immune checkpoint inhibitors.Frontiers in immunology · 2025Article
- Neutrophil Extracellular Traps (NETs) in Sterile Inflammatory Diseases.Journal of inflammation research · 2025Review
- Vagus nerve stimulation: Novel concept for the treatment of glioblastoma and solid cancers by cytokine (interleukin-6) reduction, attenuating the SASP, enhancing tumor immunity.Brain, behavior, & immunity - health · 2024Review
Corrections and comments
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Authors and funding
44 authors at 3 institutions in 2 countries.
Yifan ZhouDepartment of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0003-0975-1479
Yusra B MedikDepartment of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0003-0763-3719
Bhakti PatelDepartment of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0002-8090-0193
Daniel B ZamlerDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0003-0375-8119
Sijie ChenMinistry of Education Key Lab of Bioinformatics and Bioinformatics Division, Beijing National Research Center for Information Science and Technology; Department of Automation, Tsinghua University, Beijing, China.ORCID 0000-0003-4331-0773
Thomas ChapmanDepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0002-5723-5498
Sarah SchneiderDepartment of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0001-7027-7978
Elizabeth M ParkDepartment of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0002-1670-2299
Rachel L BabcockDepartment of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0002-1848-5494
Taylor T ChrisikosDepartment of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0001-8966-4046
Laura M KahnDepartment of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0002-6679-7599
Allison M DyevoichDepartment of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0002-4106-0435
Josue E PinedaDepartment of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0002-8132-1804
Matthew C WongPlatform for Innovative Microbiome and Translational Research, MD Anderson Cancer Center, Houston, TX.ORCID 0000-0002-6317-2526
Aditya K MishraPlatform for Innovative Microbiome and Translational Research, MD Anderson Cancer Center, Houston, TX.ORCID 0000-0003-0775-3219
Samuel H CassDepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0001-6160-2177
Alexandria P CogdillDepartment of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0001-8917-9462
Daniel H JohnsonDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0002-4778-686X
Sarah B JohnsonDepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0001-8936-0958
Khalida WaniDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0002-2383-3908
Debora A LedesmaDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0002-6670-7645
Courtney W HudgensDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0001-8312-7485
Jingjing WangDepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0002-6211-6717
Md Abdul Wadud KhanDepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0003-0596-862X
Christine B PetersonThe University of Texas MD Anderson Cancer Center, UTHealth Graduate School of Biomedical Sciences, Houston, TX.ORCID 0000-0003-3316-0468
Aron Y JoonDepartment of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0003-2615-2179
Weiyi PengDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0002-7785-6240
Haiyan S LiDepartment of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0001-5069-9735
Reetakshi AroraDepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0002-5437-4521
Ximing TangDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0001-6534-6852
Maria Gabriela RasoDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0003-2105-5556
Xuegong ZhangMinistry of Education Key Lab of Bioinformatics and Bioinformatics Division, Beijing National Research Center for Information Science and Technology; Department of Automation, Tsinghua University, Beijing, China.ORCID 0000-0002-9684-5643
Wai Chin FooDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0002-0471-4911
Michael T TetzlaffDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0001-7899-4138
Gretchen E DiehlImmunology Program, Memorial Sloan Kettering Cancer Center, New York, NY.ORCID 0000-0002-1841-2842
Karen Clise-DwyerDepartment of Hematopoietic Biology and Malignancy, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0001-9954-1197
Elizabeth M WhitleyDepartment of Veterinary Medicine and Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0001-5737-5645
Matthew M GubinDepartment of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0001-7443-2752
James P AllisonDepartment of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0001-8980-5697
Patrick HwuThe University of Texas MD Anderson Cancer Center, UTHealth Graduate School of Biomedical Sciences, Houston, TX.ORCID 0000-0002-8293-1313
Nadim J AjamiDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0002-3808-8576
Adi DiabDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0002-0153-0244
Jennifer A WargoDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0003-3438-7576
Stephanie S WatowichDepartment of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0003-1969-659X
The University of Texas MD Anderson Cancer Center · USTsinghua University · CNMemorial Sloan Kettering Cancer Center · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4MTumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8MTRAINING 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
$10.3MDefining Protective Responses in Hematopoietic Cells Mediated by STAT3 Anti-Inflammatory ActivityR01AI133822 · NIAID · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI WATOWICH, STEPHANIE S · 2018 to 2022
$2.1MRegulation and function of nonlymphoid organ CD103 dendritic cellsR01AI109294 · NIAID · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI WATOWICH, STEPHANIE S · 2015 to 2019
$2.0MThe role of the PI3K pathway in immune resistanceR01CA187076 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DAVIES, MICHAEL, HWU, PATRICK · 2014 to 2018
$2.0MNew data science approaches to visualize and understand the impact of the microbiome on risk of graft-versus-host diseaseR01HL158796 · NHLBI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI PETERSON, CHRISTINE B · 2022 to 2025
$1.0MRegulation and function of nonlymphoid organ CD103+ dendritic cellsR56AI109294 · NIAID · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI WATOWICH, STEPHANIE S · 2021 to 2021
$481kNCI NIH HHS P30 CA008748NCI NIH HHS P30 CA016672NCI NIH HHS P50 CA221703NCI NIH HHS R01 CA187076NCI NIH HHS T32 CA009599NHLBI NIH HHS R01 HL158796NIAID NIH HHS R01 AI109294NIAID NIH HHS R01 AI133822NIAID NIH HHS R56 AI109294
Abstract
Immune checkpoint blockade (ICB) has revolutionized cancer treatment, yet quality of life and continuation of therapy can be constrained by immune-related adverse events (irAEs). Limited understanding of irAE mechanisms hampers development of approaches to mitigate their damage. To address this, we examined whether mice gained sensitivity to anti-CTLA-4 (αCTLA-4)-mediated toxicity upon disruption of gut homeostatic immunity. We found αCTLA-4 drove increased inflammation and colonic tissue damage in mice with genetic predisposition to intestinal inflammation, acute gastrointestinal infection, transplantation with a dysbiotic fecal microbiome, or dextran sodium sulfate administration. We identified an immune signature of αCTLA-4-mediated irAEs, including colonic neutrophil accumulation and systemic interleukin-6 (IL-6) release. IL-6 blockade combined with antibiotic treatment reduced intestinal damage and improved αCTLA-4 therapeutic efficacy in inflammation-prone mice. Intestinal immune signatures were validated in biopsies from patients with ICB colitis. Our work provides new preclinical models of αCTLA-4 intestinal irAEs, mechanistic insights into irAE development, and potential approaches to enhance ICB efficacy while mitigating irAEs.
Indexed as
ColitisInterleukin-6AnimalsImmunotherapyInflammationMiceQuality of LifeInterleukin-6
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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.