A non-antibiotic-disrupted gut microbiome is associated with clinical responses to CD19-CAR-T cell cancer immunotherapy

Stein‐Thoeringer, Christoph K.; Saini, Neeraj; Zamir, Eli; Blumenberg, Viktoria; Schubert, Maria‐Luisa; Mor, Uria; Fante, Matthias; 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; Ahmed, Sairah; Iyer, Swaminathan Padmanabhan; Steiner, Raphaël; Jain, Preetesh; Nastoupil, Loretta J.; Westin, Jason R.; Arora, Reetakshi; Wang, Michael L.; Turner, Joel G.; Menges, Meghan; Hidalgo-Vargas, Melanie J.; 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

doi:10.1038/s41591-023-02234-6

Cited by 81 publications

(49 citation statements)

References 48 publications

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“…Another report among lymphoma patients treated with CD19-targeted chimeric antigen receptor (CAR)-T cell therapy, a higher relative abundance of Bacteroides eggerthii , Ruminococcus lactaris , Eubacterium spp. CAG 180 , Akkermansia muciniphila , and Erysipelatoclostridium ramosum increased the probability for complete remission (CR) prediction, whereas higher relative abundances of Bacteroides stercoris and others increased the probability for non-response prediction [ 32 ]. See Table 2 for details.…”

Section: Lymphomamentioning

confidence: 99%

“…An increased relative abundance of Bacteroides eggerthii , Ruminococcus lactaris , Eubacterium spp. CAG 180 , Akkermansia muciniphila , and Erysipelatoclostridium ramosum increased the probability for CR prediction was observed, whereas higher relative abundances of Bacteroides stercoris and others increased the probability for non-response prediction [ 32 ].…”

Section: Lymphomamentioning

confidence: 99%

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Intestinal Microbes and Hematological Malignancies

Zhu

Yang

et al. 2023

Cancers

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Hematological malignancies are diverse, with high malignancy characteristics, poor prognoses, and high mortality rates. The development of hematological malignancies is driven by genetic factors, tumor microenvironment factors, or metabolic factors; however, even when considering all of these factors, one still cannot fully estimate the risk of hematological malignancies. Several recent studies have demonstrated an intimate connection between intestinal microbes and the progression of hematological malignancies, and gut microbes play a primary role in the initiation and progression of hematological tumors through direct and indirect mechanisms. Thus, we summarize the correlation between intestinal microbes and hematological malignancies’ onset, progression, and therapeutic effect in order to better understand how intestinal microbes affect their initiation and progression, especially in leukemia, lymphoma, and multiple myeloma, which may provide potential therapeutic targets for improving the survival of patients with hematological malignancies.

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Section: Lymphomamentioning

confidence: 99%

Section: Lymphomamentioning

confidence: 99%

Intestinal Microbes and Hematological Malignancies

Zhu

Yang

et al. 2023

Cancers

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“…Most recent studies have further demonstrated the promise of integrating multi‐dimensional omics data to understand the determinants of CAR T cell efficacy. For example, the efficacy of CAR T cells can be enhanced through the inhibition of key immunosuppressive factor in the tumour microenvironment (TME), 8 and the composition of bacterial species of gut microbiome was also associated with the response to CAR T therapy 9 …”

Section: Figurementioning

confidence: 99%

“…For example, the efficacy of CAR T cells can be enhanced through the inhibition of key immunosuppressive factor in the tumour microenvironment (TME), 8 and the composition of bacterial species of gut microbiome was also associated with the response to CAR T therapy. 9 Finally, we summarized the factors related to CAR T cell-induced toxicities revealed by muti-omics data. These toxicities include cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome (ICANS) and on-target, off-tumour toxicities.…”

Section: Cart Omicsmentioning

confidence: 99%

A multi‐omics perspective of CAR T cell therapy

Yang

Chen

Han

2023

Clinical & Translational Med

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As omics technologies, including genomics, epigenomics, transcriptomics, T cell receptor‐repertorie profiling, proteomics, metabolomics and microbiomics, have provided valuable insights into CAR T cell therapy, in our recent review, we discuss these multidimensional profiling technologies in CAR T cell research, and their potential to identify tumor‐specific antigens and molecular characteristics associated with anti‐tumour effects and toxicities.

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“…28,29 Initial clinical evidence suggests that the gut microbiota may also influence the antitumor effects of CAR T cell therapy. [30][31][32][33] In this perspective article, we review the currently available evidence of the role of the microbiota in CART, including preclinical and clinical published data. Despite the limited current clinical evidence, we attempt to speculate on the potential therapeutic approaches that could be developed to modulate the microbiota and enhance CART efficacy and reduce toxicity.…”

mentioning

confidence: 99%

Harnessing the Gut Microbiota to Potentiate the Efficacy of CAR T Cell Therapy

Gabrielli,

Shouval,

Ghilardi

et al. 2023

HemaSphere

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A non-antibiotic-disrupted gut microbiome is associated with clinical responses to CD19-CAR-T cell cancer immunotherapy

Cited by 81 publications

References 48 publications

Intestinal Microbes and Hematological Malignancies

Intestinal Microbes and Hematological Malignancies

A multi‐omics perspective of CAR T cell therapy

Harnessing the Gut Microbiota to Potentiate the Efficacy of CAR T Cell Therapy

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