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December 8, 2025BloodOpen Access

Multi-faceted influence of immunomodulatory metabolites on CAR-T cell therapy

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Authors

MPMarkus PerlUniversity Hospital RegensburgSDSimon DelahaisLMU KlinikumGLGloria Lutzny‐GeierFriedrich-Alexander-Universität Erlangen-Nürnberg

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Overview

Research reveals gut microbiome metabolites impact CAR-T cell function and predict progression free survival in patients.

Key Points

  • This study investigates how immunomodulatory metabolites from the gut microbiome affect CAR-T cell therapy.
  • Analyzed fecal content using shotgun metagenomic sequencing and targeted mass spectrometry in CAR-T cell recipients.
  • Evaluated CAR-T cell cytotoxicity and phenotype through in vitro assays and flow cytometry.
  • Used syngeneic B-cell lymphoma mouse models to assess the impact of metabolites in vivo.
  • Conducted single-cell RNA sequencing to examine treatment-specific changes in CAR-T cells.
  • Developed a clinical risk score based on metabolite profiles to predict patient outcomes.
  • Loss of gut-derived metabolites correlated with poorer clinical outcomes and reduced progression free survival.
  • Depletion of short-chain fatty acids was linked to increased disease progression risk.
  • Identified specific metabolites impairing or enhancing CAR-T cell efficacy based on in vitro and in vivo assessments.
  • Found a four-parameter clinical risk score predicts overall survival based on metabolite levels.

Cite This Study

Perl et al. (2025) studied this question.

synapsesocial.com/papers/69362f764fa91c937236e3fahttps://doi.org/10.1182/blood-2025-2343
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Data from Microbiota Shape Metabolic and Immune Determinants of CAR-T Therapy and Correlate with Outcomes in Myeloma2025
  2. 2Microbial metabolite-guided CAR T cell engineering enhances anti-tumor immunity via epigenetic-metabolic crosstalk2024 · 14 citations
  3. 3Microbiome and metabolite biomarkers of CAR T-cell therapy outcomes in relapsed/refractory diffuse large B cell lymphoma2025 · 5 citations
  4. 4The Gut Microbiome Drives Endogenous T Cell Activation Following CAR-T Cell Therapy2026
  5. 5The Potential of the Gut Microbiota and Butyrate to Enhance CAR-T Cell Therapy in Non-Hodgkin Lymphoma2025