Metabolic activity of gut bacteria can either promote or inhibit function of CAR T cells in cancer therapy
Immunotherapies, especially CAR T-cell therapy, have fundamentally changed cancer treatment in recent years, particularly for certain forms of leukemia and lymphoma. Yet not all tumors respond equally well, and the reasons for this remain incompletely understood. A new multicenter study by the Leibniz Institute for Immunotherapy collaboration group, Innate Immune Sensing in Cancer and…
A recent study reveals that gut bacteria's metabolic activity can either enhance or hinder the effectiveness of CAR T-cell therapy in cancer treatment. Conducted by researchers at the Leibniz Institute for Immunotherapy and involving 129 patients across three German university hospitals, the study found that specific microbial metabolites play a crucial role in treatment outcomes.
Low levels of short-chain fatty acid valerate before treatment were associated with a higher risk of disease progression, while therapeutic administration of this metabolite improved CAR T-cell function in both human and mouse models. Conversely, elevated levels of indole metabolites, such as indole-3-carboxaldehyde and indole-3-acetic acid, were linked to unfavorable outcomes, reducing CAR T-cell efficacy.
The complex role of these metabolites extends beyond just influencing the therapeutic immune system; they can also have tumor-promoting effects. The research challenges the conventional view that microbiome composition is the primary determinant of CAR T-cell therapy success and opens up new avenues for microbiome-based therapies.
Future studies aim to validate the findings and explore the potential of targeting these metabolites to improve treatment outcomes.
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