دورية أكاديمية
Gut microbiome correlates of response and toxicity following anti-CD19 CAR T cell therapy.
| العنوان: | Gut microbiome correlates of response and toxicity following anti-CD19 CAR T cell therapy. |
|---|---|
| المؤلفون: | Smith M; Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Department of Medicine, Weill Cornell Medical College, New York, NY, USA.; Cellular Therapeutics Center, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University School of Medicine, Stanford, CA, USA., Dai A; Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Ghilardi G; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.; Division of Hematology-Oncology, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA., Amelsberg KV; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.; Division of Hematology-Oncology, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA., Devlin SM; Department of Biostatistics and Epidemiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Pajarillo R; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.; Division of Hematology-Oncology, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA., Slingerland JB; Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Beghi S; Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA., Herrera PS; Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Weill Cornell Medical College, New York, NY, USA., Giardina P; Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Clurman A; Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Dwomoh E; Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Armijo G; Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Gomes ALC; Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Littmann ER; The Duchossois Family Institute, University of Chicago, Chicago, IL, USA., Schluter J; Institute for Computational Medicine, New York University Langone Health, New York, NY, USA., Fontana E; Molecular Microbiology Core Facility, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Taur Y; Infectious Disease Service, Department of Medicine, and Immunology Program, Sloan Kettering Institute, New York, NY, USA., Park JH; Department of Medicine, Weill Cornell Medical College, New York, NY, USA.; Cellular Therapeutics Center, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Palomba ML; Department of Medicine, Weill Cornell Medical College, New York, NY, USA.; Cellular Therapeutics Center, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Halton E; Cellular Therapeutics Center, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Department of Nursing, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Ruiz J; Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Jain T; Division of Hematologic Malignancies and Bone Marrow Transplantation, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA., Pennisi M; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy., Afuye AO; Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Perales MA; Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Department of Medicine, Weill Cornell Medical College, New York, NY, USA., Freyer CW; Department of Pharmacy, Hospital of the University of Pennsylvania, Philadelphia, PA, USA., Garfall A; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA., Gier S; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA., Nasta S; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.; Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA., Landsburg D; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.; Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA., Gerson J; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.; Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA., Svoboda J; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.; Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA., Cross J; The Donald B. and Catherine C. Marron Cancer Metabolism Center, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Chong EA; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.; Division of Hematology-Oncology, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.; Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA., Giralt S; Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Department of Medicine, Weill Cornell Medical College, New York, NY, USA., Gill SI; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.; Division of Hematology-Oncology, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA., Riviere I; Cellular Therapeutics Center, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Porter DL; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.; Division of Hematology-Oncology, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA., Schuster SJ; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.; Division of Hematology-Oncology, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.; Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA., Sadelain M; Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Frey N; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.; Division of Hematology-Oncology, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA., Brentjens RJ; Department of Medicine, Weill Cornell Medical College, New York, NY, USA.; Cellular Therapeutics Center, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, NY, USA., June CH; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.; Department of Pathology and Laboratory Medicine, Perelman School of Medicine University of Pennsylvania, Philadelphia, PA, USA., Pamer EG; The Duchossois Family Institute, University of Chicago, Chicago, IL, USA., Peled JU; Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Department of Medicine, Weill Cornell Medical College, New York, NY, USA., Facciabene A; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA. facciabe@pennmedicine.upenn.edu.; Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. facciabe@pennmedicine.upenn.edu.; Ovarian Cancer Research Center, University of Pennsylvania, Philadelphia, PA, USA. facciabe@pennmedicine.upenn.edu., van den Brink MRM; Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. vandenbm@mskcc.org.; Department of Immunology, Sloan Kettering Institute, New York, NY, USA. vandenbm@mskcc.org., Ruella M; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA. mruella@upenn.edu.; Division of Hematology-Oncology, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. mruella@upenn.edu.; Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. mruella@upenn.edu. |
| المصدر: | Nature medicine [Nat Med] 2022 Apr; Vol. 28 (4), pp. 713-723. Date of Electronic Publication: 2022 Mar 14. |
| نوع المنشور: | Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Publishing Company Country of Publication: United States NLM ID: 9502015 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1546-170X (Electronic) Linking ISSN: 10788956 NLM ISO Abbreviation: Nat Med Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: New York Ny : Nature Publishing Company Original Publication: New York, NY : Nature Pub. Co., [1995- |
| مواضيع طبية MeSH: | Gastrointestinal Microbiome* , Neurotoxicity Syndromes*/etiology , Receptors, Chimeric Antigen*, Antigens, CD19 ; Humans ; Immunotherapy, Adoptive/adverse effects ; Prospective Studies ; Retrospective Studies |
| مستخلص: | 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. (© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.) |
| التعليقات: | Comment in: Med. 2022 May 13;3(5):281-283. (PMID: 35584646) Erratum in: Nat Med. 2023 Nov;29(11):2954. (PMID: 36253610) |
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| معلومات مُعتمدة: | R01 CA226983 United States CA NCI NIH HHS; P01 CA214278 United States CA NCI NIH HHS; P01 CA023766 United States CA NCI NIH HHS; R01 HL147584 United States HL NHLBI NIH HHS; R01 CA219871 United States CA NCI NIH HHS; R01 HL125571 United States HL NHLBI NIH HHS; K99 CA212302 United States CA NCI NIH HHS; K08 CA194256 United States CA NCI NIH HHS; R01 CA228358 United States CA NCI NIH HHS; R00 CA212302 United States CA NCI NIH HHS; K08 HL143189 United States HL NHLBI NIH HHS; R01 HL123340 United States HL NHLBI NIH HHS; R01 CA206012 United States CA NCI NIH HHS; R01 CA228308 United States CA NCI NIH HHS; P30 CA008748 United States CA NCI NIH HHS; P01 AG052359 United States AG NIA NIH HHS |
| المشرفين على المادة: | 0 (Antigens, CD19) 0 (Receptors, Chimeric Antigen) |
| تواريخ الأحداث: | Date Created: 20220315 Date Completed: 20220421 Latest Revision: 20240227 |
| رمز التحديث: | 20240227 |
| مُعرف محوري في PubMed: | PMC9434490 |
| DOI: | 10.1038/s41591-022-01702-9 |
| PMID: | 35288695 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1546-170X |
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| DOI: | 10.1038/s41591-022-01702-9 |