Research evaluating patients undergoing CAR-T cell therapy reveals that the taxonomic composition of the gut microbiome is a poor indicator of therapeutic success, whereas gut immunomodulatory metabolites strongly influence clinical outcomes. Through metagenomic and metabolomic analyses, investigators discovered that short-chain fatty acids, particularly valeric acid, enhance T-cell function, fitness, and tumor control. Conversely, indole derivatives and branched-chain fatty acids like isovaleric acid impair CAR-T cell efficacy and promote tumor growth. Furthermore, antibiotic exposure prior to treatment diminishes beneficial microbial metabolites and correlates with decreased progression-free survival. These findings highlight that targeting microbial metabolism offers a promising strategy to predict and improve the efficacy of immunotherapy.
References:
Perl M, Guetter S, Shah D, et al. Opposing functions of gut immunomodulatory metabolites on CAR-T therapy[J]. Cell, 2026.
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