Abstract
The microbiome is a key regulator of host homeostasis and immune activity, in part through the production of metabolites. These microbiota-derived metabolites can modulate both the innate and adaptive immune system, as well as directly target tumour cells, thereby regulating anti-tumour immunity and response to immunotherapy. Here, we describe the current mechanistic knowledge on how these metabolites exert their effects and outline the methodologies used to detect and assess these metabolites. Finally, we summarize microbiota-targeted therapies capable of improving microbial functionality to ultimately enhance immunotherapy responses and improve patient survival.
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Acknowledgements
We sincerely acknowledge Mrs Anneke Hoogendijk and the Foundation Weteringschans for their generous support, which has enabled our investigation of the role of the microbiome in cancer immunotherapy responses.
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C. Toner-Bartelds and I. L. Mimpen contributed equally to the preparation of this manuscript. C. Toner-Bartelds: conceptualisation, investigation, writing—original draft preparation, review, and editing. I. L. Mimpen: conceptualisation, investigation, writing—original draft preparation, review, and editing. M. Parra-Martinez: investigation, writing—original draft preparation, review, and editing. B. M. T. Burgering: assistance with revisions and writing—review. E. Voest: conceptualisation, supervision, funding acquisition and writing—review and editing.
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E. Voest is the founder and current member of the supervisory board of the Hartwig Medical Foundation, an independent non-executive director and shareholder of Sanofi, a co-founder and shareholder of Mosaic Therapeutics, and a board member and founder of the Centre for Personalised Cancer Treatment. He has received clinical study grants from Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Clovis, Eisai, Eli Lilly, GSK, Ipsen, Johnson & Johnson, MSD, Novartis, Pfizer, Roche, Servier, Incyte, MRM Health and Sanofi, all paid to the Netherlands Cancer Institute. C. Toner-Bartelds, I. Mimpen, M. Parra-Martinez and B. Burgering declare no competing interests.
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Toner-Bartelds, C., Mimpen, I.L., Parra-Martinez, M. et al. Microbiota-derived metabolites as modulators of cancer immunotherapy response. Nat Commun (2026). https://doi.org/10.1038/s41467-026-72178-1
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DOI: https://doi.org/10.1038/s41467-026-72178-1
