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| 001 | 304439 | ||
| 005 | 20250907022549.0 | ||
| 024 | 7 | _ | |a 10.1158/2159-8290.CD-24-1230 |2 doi |
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| 100 | 1 | _ | |a Marcos-Kovandzic, Laura |0 0009-0002-6866-5300 |b 0 |
| 245 | _ | _ | |a Gut Microbiota Modulation through Akkermansia spp. Supplementation Increases CAR T-cell Potency. |
| 260 | _ | _ | |a Philadelphia, Pa. |c 2025 |b [Verlag nicht ermittelbar] |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1757078043_959 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a This study investigates the clinical relevance of the gut microbiome at taxonomic and metabolic levels in anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, both in patients and in a preclinical syngeneic tumor model. Patients with B-cell lymphoma treated with CD19 CAR T cells exhibited profound intestinal dysbiosis, exacerbated after CAR T-cell infusion. This dysbiosis was characterized by low bacterial richness, low soluble MAdCAM-1, and loss of Akkermansia species, associated with resistance to therapy. Mechanistically, oral Akkermansia massiliensis supplementation increased CAR T-cell infiltration into the bone marrow, inverted the CD4/CD8 CAR T-cell ratio, favored Tc1 CD8+ T-cell polarization, and promoted the release of tryptophan-derived indole metabolites, leading to better tumor control. The clinical benefit of Akkermansia spp. supplementation was abolished when CAR T cells were genetically deficient in the indole receptor, aryl hydrocarbon receptor (AhR). AhR-agonistic indoles alone failed to replicate the bacterium's anticancer effects. These findings suggest that Akkermansia supplementation could improve CAR T-cell potency in patients with intestinal Akkermansia deficiency.B-cell lymphoma patients treated with CAR T cells harbor major gut microbiota perturbations and related metabolism that restrain CAR T-cell therapy. Reprogramming the gut microbiota ecosystem by oral A. massiliensis supplementation induces CAR T-cell niching and Tc1 differentiation in the bone marrow, promoting tumor control in an AhR-dependent manner. |
| 536 | _ | _ | |a 899 - ohne Topic (POF4-899) |0 G:(DE-HGF)POF4-899 |c POF4-899 |f POF IV |x 0 |
| 588 | _ | _ | |a Dataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de |
| 650 | _ | 7 | |a Receptors, Aryl Hydrocarbon |2 NLM Chemicals |
| 650 | _ | 7 | |a Receptors, Chimeric Antigen |2 NLM Chemicals |
| 650 | _ | 7 | |a Antigens, CD19 |2 NLM Chemicals |
| 650 | _ | 2 | |a Gastrointestinal Microbiome: immunology |2 MeSH |
| 650 | _ | 2 | |a Humans |2 MeSH |
| 650 | _ | 2 | |a Mice |2 MeSH |
| 650 | _ | 2 | |a Animals |2 MeSH |
| 650 | _ | 2 | |a Akkermansia: immunology |2 MeSH |
| 650 | _ | 2 | |a Immunotherapy, Adoptive: methods |2 MeSH |
| 650 | _ | 2 | |a Receptors, Aryl Hydrocarbon: metabolism |2 MeSH |
| 650 | _ | 2 | |a Receptors, Chimeric Antigen: immunology |2 MeSH |
| 650 | _ | 2 | |a Receptors, Chimeric Antigen: metabolism |2 MeSH |
| 650 | _ | 2 | |a Female |2 MeSH |
| 650 | _ | 2 | |a Lymphoma, B-Cell: therapy |2 MeSH |
| 650 | _ | 2 | |a Lymphoma, B-Cell: immunology |2 MeSH |
| 650 | _ | 2 | |a Lymphoma, B-Cell: microbiology |2 MeSH |
| 650 | _ | 2 | |a Dysbiosis |2 MeSH |
| 650 | _ | 2 | |a Male |2 MeSH |
| 650 | _ | 2 | |a Antigens, CD19: immunology |2 MeSH |
| 700 | 1 | _ | |a Avagliano, Michele |0 0009-0000-1272-4119 |b 1 |
| 700 | 1 | _ | |a Ben Khelil, Myriam |0 0000-0003-4290-4262 |b 2 |
| 700 | 1 | _ | |a Srikanthan, Janesa |0 0009-0004-7588-7432 |b 3 |
| 700 | 1 | _ | |a Abdallah, Rim |0 0000-0001-5061-5554 |b 4 |
| 700 | 1 | _ | |a Petrocelli, Valentina |0 0000-0002-8066-870X |b 5 |
| 700 | 1 | _ | |a Rengassamy, Jessica |0 0009-0006-6372-4075 |b 6 |
| 700 | 1 | _ | |a Alfaro, Alexia |0 0009-0009-1802-5103 |b 7 |
| 700 | 1 | _ | |a Bied, Mathilde |0 0009-0002-0647-8964 |b 8 |
| 700 | 1 | _ | |a Fidelle, Marine |0 0000-0002-5589-9688 |b 9 |
| 700 | 1 | _ | |a Ferrere, Gladys |0 0000-0001-6103-9185 |b 10 |
| 700 | 1 | _ | |a Daillère, Romain |0 0000-0003-3617-6377 |b 11 |
| 700 | 1 | _ | |a Arbab, Ahmadreza |0 0000-0002-7015-0448 |b 12 |
| 700 | 1 | _ | |a Amine-Hneineh, Roula |0 0009-0003-1983-6684 |b 13 |
| 700 | 1 | _ | |a Pages, Arnaud |0 0000-0002-2337-8693 |b 14 |
| 700 | 1 | _ | |a Dartigues, Peggy |0 0009-0002-8383-3050 |b 15 |
| 700 | 1 | _ | |a Ly, Pierre |0 0000-0001-9541-5986 |b 16 |
| 700 | 1 | _ | |a Simon, Sylvain |0 0000-0001-5985-3946 |b 17 |
| 700 | 1 | _ | |a Durand, Sylvère |0 0000-0001-6356-1006 |b 18 |
| 700 | 1 | _ | |a Gottschlich, Adrian |0 0000-0002-2898-4182 |b 19 |
| 700 | 1 | _ | |a Ginhoux, Florent |0 0000-0002-2857-7755 |b 20 |
| 700 | 1 | _ | |a Blériot, Camille |0 0000-0002-4298-2888 |b 21 |
| 700 | 1 | _ | |a Liu, Peng |b 22 |
| 700 | 1 | _ | |a Zhao, Liwei |0 0000-0001-5077-327X |b 23 |
| 700 | 1 | _ | |a Creusot, Laura |0 0000-0002-3882-8423 |b 24 |
| 700 | 1 | _ | |a Rolhion, Nathalie |0 0000-0002-2946-4808 |b 25 |
| 700 | 1 | _ | |a Derosa, Lisa |b 26 |
| 700 | 1 | _ | |a Kroemer, Guido |0 0000-0002-9334-4405 |b 27 |
| 700 | 1 | _ | |a Menger, Laurie |0 0000-0003-0949-6607 |b 28 |
| 700 | 1 | _ | |a Kobold, Sebastian |0 0000-0002-5612-4673 |b 29 |
| 700 | 1 | _ | |a Castilla-Llorente, Cristina |0 0000-0002-7728-5804 |b 30 |
| 700 | 1 | _ | |a Sokol, Harry |0 0000-0002-2914-1822 |b 31 |
| 700 | 1 | _ | |a Casola, Stefano |0 0000-0001-5580-0986 |b 32 |
| 700 | 1 | _ | |a Pasolli, Edoardo |0 0000-0003-0799-3490 |b 33 |
| 700 | 1 | _ | |a Zitvogel, Laurence |0 0000-0003-1596-0998 |b 34 |
| 700 | 1 | _ | |a Bigenwald, Camille |0 0000-0003-2714-2087 |b 35 |
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