Longitudinal gut microbiome changes in immune checkpoint blockade-treated advanced melanoma
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Authors
Björk, J. R.Bolte, L. A.
Thomas, A. M.
Lee, K. A.
Rossi, N.
Wind, T. T.
Smit, L. M.
Armanini, F.
Asnicar, F.
Blanco-Miguez, A.
Board, R.
Calbet-Llopart, N.
Derosa, L.
Dhomen, N.
Brooks, K.
Harland, M.
Harries, M.
Lorigan, Paul
Manghi, P.
Marais, Richard
Newton-Bishop, J.
Nezi, L.
Pinto, F.
Potrony, M.
Puig, S.
Serra-Bellver, P.
Shaw, H. M.
Tamburini, S.
Valpione, S.
Waldron, L.
Zitvogel, L.
Zolfo, M.
de Vries, E. G. E.
Nathan, P.
Fehrmann, R. S. N.
Spector, T. D.
Bataille, V.
Segata, N.
Hospers, G. A. P.
Weersma, R. K.
Affiliation
The Christie NHS Foundation Trust, Manchester, UK; Division of Cancer Sciences, University of Manchester, Manchester, UK; Molecular Oncology Group, Cancer Research UK Manchester Institute, University of Manchester, Manchester, UKIssue Date
2024
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Multiple clinical trials targeting the gut microbiome are being conducted to optimize treatment outcomes for immune checkpoint blockade (ICB). To improve the success of these interventions, understanding gut microbiome changes during ICB is urgently needed. Here through longitudinal microbiome profiling of 175 patients treated with ICB for advanced melanoma, we show that several microbial species-level genome bins (SGBs) and pathways exhibit distinct patterns from baseline in patients achieving progression-free survival (PFS) of 12 months or longer (PFS >= 12) versus patients with PFS shorter than 12 months (PFS <12). Out of 99 SGBs that could discriminate between these two groups, 20 were differentially abundant only at baseline, while 42 were differentially abundant only after treatment initiation. We identify five and four SGBs that had consistently higher abundances in patients with PFS >= 12 and <12 months, respectively. Constructing a log ratio of these SGBs, we find an association with overall survival. Finally, we find different microbial dynamics in different clinical contexts including the type of ICB regimen, development of immune-related adverse events and concomitant medication use. Insights into the longitudinal dynamics of the gut microbiome in association with host factors and treatment regimens will be critical for guiding rational microbiome-targeted therapies aimed at enhancing ICB efficacy.Citation
Björk JR, Bolte LA, Thomas AM, Lee KA, Rossi N, Wind TT, et al. Longitudinal gut microbiome changes in immune checkpoint blockade-treated advanced melanoma. Nature medicine. 2024 2024 FEB 16. PubMed PMID: WOS:001163654900001. English.Journal
Nature MedicineDOI
10.1038/s41591-024-02803-3PubMed ID
38365950Additional Links
https://dx.doi.org/10.1038/s41591-024-02803-3Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1038/s41591-024-02803-3
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