16/01-2023 - Christoph STEIN-THOERINGER : On the role of the gut microbiome in the efficacy of CAR-T cell immunotherapy

LES LUNDIS DE SAINT-ANTOINE

Bâtiment Kourilsky - 13h–14h

Salle des Conférences (Rez de Chaussée),

184 rue du Faubourg Saint-Antoine, Paris

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LUNDI 09 JANVIER 2023

On the role of the gut microbiome in the efficacy of CAR-T cell immunotherapy

Christoph STEIN-THOERINGER

Professor for Infectious Diseases and Translational Microbiome Sciences - Internal Medicine I, University Clinic Tuebingen Infectious Disease Section and Translational Microbiome Lab

invitée par Equipe de Mohamad MOTHY (Equipe MOTHY (florent.malard@yahoo.fr))

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The gut microbiome and factors such as antibiotics or diet affecting its composition are increasingly recognized to affect the efficacy and toxicity of immunotherapies. Treatment with CD19-directed chimeric antigen receptor T cells (CARTs) represents a novel approach in cancer therapy that aims to boost antitumor immunity against relapsed or progressive lymphoid malignancies. Following previous studies on the importance of the gut microbiome in adoptive T cell transfer therapies, we performed an international, multicentric clinical trial with centers in Germany and the US studying the effects of antibiotic treatment and gut microbiome features associated with clinical outcomes. In synopsis, we observed that broad-spectrum antibiotic administration shortly before or around CAR-T cell infusion significantly reduces overall survival and increase the incidence of tumor progression in lymphoma patients. Despite an association with microbiome dysbiosis, antibiotic treatment is identified as a surrogate for disease severity and an increased inflammatory state; it significantly interferes with the ability of microbiome features to predict clinical outcomes applying AI algorithms. However, excluding these events from our machine-learning analyses uncovers a specific gut microbiome signature at baseline that is able to segregate long-term response to CAR-T immunotherapy. We also found that a specific microbiome signature is associated with CAR-T cell expansion, persistence and exhaustion phenotypes along changes in the serum cytokine milieu.
Despite a clear mechanisms provided, we can show for the first time the there is an intricate relationship between a patient’s microbiome and the efficacy of CAR-T cells against lymphoma providing the necessity for “microbiome stewardship” in cancer patients.

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