Stein-Thoeringer, Christoph K. and Saini, Neeraj Y. and Zamir, Eli and Blumenberg, Viktoria and Schubert, Maria-Luisa and Mor, Uria and Fante, Matthias A. and Schmidt, Sabine and Hayase, Eiko and Hayase, Tomo and Rohrbach, Roman and Chang, Chia-Chi and McDaniel, Lauren and Flores, Ivonne and Gaiser, Rogier and Edinger, Matthias and Wolff, Daniel and Heidenreich, Martin and Strati, Paolo and Nair, Ranjit and Chihara, Dai and Fayad, Luis E. and Ahmed, Sairah and Iyer, Swaminathan P. and Steiner, Raphael E. and Jain, Preetesh and Nastoupil, Loretta J. and Westin, Jason and Arora, Reetakshi and Wang, Michael L. and Turner, Joel and Menges, Meghan and Hidalgo-Vargas, Melanie and Reid, Kayla and Dreger, Peter and Schmitt, Anita and Mueller-Tidow, Carsten and Locke, Frederick L. and Davila, Marco L. and Champlin, Richard E. and Flowers, Christopher R. and Shpall, Elizabeth J. and Poeck, Hendrik and Neelapu, Sattva S. and Schmitt, Michael and Subklewe, Marion and Jain, Michael D. and Jenq, Robert R. and Elinav, Eran (2023) A non-antibiotic-disrupted gut microbiome is associated with clinical responses to CD19-CAR-T cell cancer immunotherapy. NATURE MEDICINE, 29 (4). ISSN 1078-8956, 1546-170X
Full text not available from this repository. (Request a copy)Abstract
Conserved microbiome features across clinical and geographical variations may enable microbiome-based predictions of outcomes in CD19-targeted CAR-T cell immunotherapy Increasing evidence suggests that the gut microbiome may modulate the efficacy of cancer immunotherapy. In a B cell lymphoma patient cohort from five centers in Germany and the United States (Germany, n = 66; United States, n = 106; total, n = 172), we demonstrate that wide-spectrum antibiotics treatment ('high-risk antibiotics') prior to CD19-targeted chimeric antigen receptor (CAR)-T cell therapy is associated with adverse outcomes, but this effect is likely to be confounded by an increased pretreatment tumor burden and systemic inflammation in patients pretreated with high-risk antibiotics. To resolve this confounding effect and gain insights into antibiotics-masked microbiome signals impacting CAR-T efficacy, we focused on the high-risk antibiotics non-exposed patient population. Indeed, in these patients, significant correlations were noted between pre-CAR-T infusion Bifidobacterium longum and microbiome-encoded peptidoglycan biosynthesis, and CAR-T treatment-associated 6-month survival or lymphoma progression. Furthermore, predictive pre-CAR-T treatment microbiome-based machine learning algorithms trained on the high-risk antibiotics non-exposed German cohort and validated by the respective US cohort robustly segregated long-term responders from non-responders. Bacteroides, Ruminococcus, Eubacterium and Akkermansia were most important in determining CAR-T responsiveness, with Akkermansia also being associated with pre-infusion peripheral T cell levels in these patients. Collectively, we identify conserved microbiome features across clinical and geographical variations, which may enable cross-cohort microbiome-based predictions of outcomes in CAR-T cell immunotherapy.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | THERAPY; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 09 Apr 2024 09:35 |
| Last Modified: | 09 Apr 2024 09:35 |
| URI: | https://pred.uni-regensburg.de/id/eprint/60766 |
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