000304439 001__ 304439
000304439 005__ 20250907022549.0
000304439 0247_ $$2doi$$a10.1158/2159-8290.CD-24-1230
000304439 0247_ $$2pmid$$apmid:40498998
000304439 0247_ $$2pmc$$apmc:PMC12409280
000304439 0247_ $$2ISSN$$a2159-8274
000304439 0247_ $$2ISSN$$a2159-8290
000304439 0247_ $$2altmetric$$aaltmetric:178036104
000304439 037__ $$aDKFZ-2025-01852
000304439 041__ $$aEnglish
000304439 082__ $$a610
000304439 1001_ $$00009-0002-6866-5300$$aMarcos-Kovandzic, Laura$$b0
000304439 245__ $$aGut Microbiota Modulation through Akkermansia spp. Supplementation Increases CAR T-cell Potency.
000304439 260__ $$aPhiladelphia, Pa.$$b[Verlag nicht ermittelbar]$$c2025
000304439 3367_ $$2DRIVER$$aarticle
000304439 3367_ $$2DataCite$$aOutput Types/Journal article
000304439 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1757078043_959
000304439 3367_ $$2BibTeX$$aARTICLE
000304439 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000304439 3367_ $$00$$2EndNote$$aJournal Article
000304439 520__ $$aThis 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.
000304439 536__ $$0G:(DE-HGF)POF4-899$$a899 - ohne Topic (POF4-899)$$cPOF4-899$$fPOF IV$$x0
000304439 588__ $$aDataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de
000304439 650_7 $$2NLM Chemicals$$aReceptors, Aryl Hydrocarbon
000304439 650_7 $$2NLM Chemicals$$aReceptors, Chimeric Antigen
000304439 650_7 $$2NLM Chemicals$$aAntigens, CD19
000304439 650_2 $$2MeSH$$aGastrointestinal Microbiome: immunology
000304439 650_2 $$2MeSH$$aHumans
000304439 650_2 $$2MeSH$$aMice
000304439 650_2 $$2MeSH$$aAnimals
000304439 650_2 $$2MeSH$$aAkkermansia: immunology
000304439 650_2 $$2MeSH$$aImmunotherapy, Adoptive: methods
000304439 650_2 $$2MeSH$$aReceptors, Aryl Hydrocarbon: metabolism
000304439 650_2 $$2MeSH$$aReceptors, Chimeric Antigen: immunology
000304439 650_2 $$2MeSH$$aReceptors, Chimeric Antigen: metabolism
000304439 650_2 $$2MeSH$$aFemale
000304439 650_2 $$2MeSH$$aLymphoma, B-Cell: therapy
000304439 650_2 $$2MeSH$$aLymphoma, B-Cell: immunology
000304439 650_2 $$2MeSH$$aLymphoma, B-Cell: microbiology
000304439 650_2 $$2MeSH$$aDysbiosis
000304439 650_2 $$2MeSH$$aMale
000304439 650_2 $$2MeSH$$aAntigens, CD19: immunology
000304439 7001_ $$00009-0000-1272-4119$$aAvagliano, Michele$$b1
000304439 7001_ $$00000-0003-4290-4262$$aBen Khelil, Myriam$$b2
000304439 7001_ $$00009-0004-7588-7432$$aSrikanthan, Janesa$$b3
000304439 7001_ $$00000-0001-5061-5554$$aAbdallah, Rim$$b4
000304439 7001_ $$00000-0002-8066-870X$$aPetrocelli, Valentina$$b5
000304439 7001_ $$00009-0006-6372-4075$$aRengassamy, Jessica$$b6
000304439 7001_ $$00009-0009-1802-5103$$aAlfaro, Alexia$$b7
000304439 7001_ $$00009-0002-0647-8964$$aBied, Mathilde$$b8
000304439 7001_ $$00000-0002-5589-9688$$aFidelle, Marine$$b9
000304439 7001_ $$00000-0001-6103-9185$$aFerrere, Gladys$$b10
000304439 7001_ $$00000-0003-3617-6377$$aDaillère, Romain$$b11
000304439 7001_ $$00000-0002-7015-0448$$aArbab, Ahmadreza$$b12
000304439 7001_ $$00009-0003-1983-6684$$aAmine-Hneineh, Roula$$b13
000304439 7001_ $$00000-0002-2337-8693$$aPages, Arnaud$$b14
000304439 7001_ $$00009-0002-8383-3050$$aDartigues, Peggy$$b15
000304439 7001_ $$00000-0001-9541-5986$$aLy, Pierre$$b16
000304439 7001_ $$00000-0001-5985-3946$$aSimon, Sylvain$$b17
000304439 7001_ $$00000-0001-6356-1006$$aDurand, Sylvère$$b18
000304439 7001_ $$00000-0002-2898-4182$$aGottschlich, Adrian$$b19
000304439 7001_ $$00000-0002-2857-7755$$aGinhoux, Florent$$b20
000304439 7001_ $$00000-0002-4298-2888$$aBlériot, Camille$$b21
000304439 7001_ $$aLiu, Peng$$b22
000304439 7001_ $$00000-0001-5077-327X$$aZhao, Liwei$$b23
000304439 7001_ $$00000-0002-3882-8423$$aCreusot, Laura$$b24
000304439 7001_ $$00000-0002-2946-4808$$aRolhion, Nathalie$$b25
000304439 7001_ $$aDerosa, Lisa$$b26
000304439 7001_ $$00000-0002-9334-4405$$aKroemer, Guido$$b27
000304439 7001_ $$00000-0003-0949-6607$$aMenger, Laurie$$b28
000304439 7001_ $$00000-0002-5612-4673$$aKobold, Sebastian$$b29
000304439 7001_ $$00000-0002-7728-5804$$aCastilla-Llorente, Cristina$$b30
000304439 7001_ $$00000-0002-2914-1822$$aSokol, Harry$$b31
000304439 7001_ $$00000-0001-5580-0986$$aCasola, Stefano$$b32
000304439 7001_ $$00000-0003-0799-3490$$aPasolli, Edoardo$$b33
000304439 7001_ $$00000-0003-1596-0998$$aZitvogel, Laurence$$b34
000304439 7001_ $$00000-0003-2714-2087$$aBigenwald, Camille$$b35
000304439 773__ $$0PERI:(DE-600)2607892-2$$a10.1158/2159-8290.CD-24-1230$$gVol. 15, no. 9, p. 1905 - 1926$$n9$$p1905 - 1926$$tCancer discovery$$v15$$x2159-8274$$y2025
000304439 909CO $$ooai:inrepo02.dkfz.de:304439$$pVDB
000304439 9101_ $$0I:(DE-588b)2036810-0$$60000-0002-2898-4182$$aDeutsches Krebsforschungszentrum$$b19$$kDKFZ
000304439 9101_ $$0I:(DE-588b)2036810-0$$60000-0002-5612-4673$$aDeutsches Krebsforschungszentrum$$b29$$kDKFZ
000304439 9131_ $$0G:(DE-HGF)POF4-899$$1G:(DE-HGF)POF4-890$$2G:(DE-HGF)POF4-800$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bProgrammungebundene Forschung$$lohne Programm$$vohne Topic$$x0
000304439 9141_ $$y2025
000304439 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bCANCER DISCOV : 2022$$d2024-12-05
000304439 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2024-12-05
000304439 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2024-12-05
000304439 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2024-12-05
000304439 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2024-12-05
000304439 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2024-12-05
000304439 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2024-12-05
000304439 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2024-12-05
000304439 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2024-12-05
000304439 915__ $$0StatID:(DE-HGF)9925$$2StatID$$aIF >= 25$$bCANCER DISCOV : 2022$$d2024-12-05
000304439 9201_ $$0I:(DE-He78)MU01-20160331$$kMU01$$lDKTK Koordinierungsstelle München$$x0
000304439 980__ $$ajournal
000304439 980__ $$aVDB
000304439 980__ $$aI:(DE-He78)MU01-20160331
000304439 980__ $$aUNRESTRICTED