; Blumenberg, Viktoria
; Schubert, Maria-Luisa
; Mor, Uria
; Fante, Matthias A. ; Schmidt, Sabine ; Hayase, Eiko ; Hayase, Tomo ; Rohrbach, Roman ; Chang, Chia-Chi ; McDaniel, Lauren ; Flores, Ivonne ; Gaiser, Rogier ; Edinger, Matthias ; Wolff, Daniel ; Heidenreich, Martin ; Strati, Paolo ; Nair, Ranjit ; Chihara, Dai ; Fayad, Luis E. ; Ahmed, Sairah ; Iyer, Swaminathan P. ; Steiner, Raphael E. ; Jain, Preetesh
; Nastoupil, Loretta J. ; Westin, Jason ; Arora, Reetakshi ; Wang, Michael L. ; Turner, Joel ; Menges, Meghan ; Hidalgo-Vargas, Melanie ; Reid, Kayla ; Dreger, Peter ; Schmitt, Anita ; Müller-Tidow, Carsten ; Locke, Frederick L. ; Davila, Marco L.
; Champlin, Richard E. ; Flowers, Christopher R. ; Shpall, Elizabeth J. ; Poeck, Hendrik ; Neelapu, Sattva S. ; Schmitt, Michael ; Subklewe, Marion ; Jain, Michael D.
; Jenq, Robert R.
; Elinav, Eran | Dokumentenart: | Artikel | ||||
|---|---|---|---|---|---|
| Titel eines Journals oder einer Zeitschrift: | Nature Medicine | ||||
| Verlag: | NATURE PORTFOLIO | ||||
| Ort der Veröffentlichung: | BERLIN | ||||
| Band: | 29 | ||||
| Nummer des Zeitschriftenheftes oder des Kapitels: | 4 | ||||
| Seitenbereich: | S. 906-916 | ||||
| Datum: | 2023 | ||||
| Institutionen: | Medizin > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) | ||||
| Identifikationsnummer: |
| ||||
| Stichwörter / Keywords: | THERAPY; | ||||
| Dewey-Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin | ||||
| Status: | Veröffentlicht | ||||
| Begutachtet: | Ja, diese Version wurde begutachtet | ||||
| An der Universität Regensburg entstanden: | Ja | ||||
| Dokumenten-ID: | 76181 |
Zusammenfassung
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 = ...

Zusammenfassung
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.
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