Influence of microbiota-associated metabolic reprogramming on clinical outcome in patients with melanoma from the randomized adjuvant dendritic cell-based MIND-DC trial
Alves Costa Silva, Carolina; Piccinno, Gianmarco; Suissa, Déborah; Bourgin, Mélanie; Schreibelt, Gerty; Durand, Sylvère; Birebent, Roxanne; Fidelle, Marine; Sow, Cissé; Aprahamian, Fanny; Manghi, Paolo; Punčochář, Michal; Asnicar, Francesco; Pinto, Federica; Armanini, Federica; Terrisse, Safae; Routy, Bertrand; Drubay, Damien; Eggermont, Alexander M.M.; Kroemer, Guido; Segata, Nicola; Zitvogel, Laurence; Derosa, Lisa; Bol, Kalijn F.; de Vries, I. Jolanda M.
(2024) Nature Communications, volume 15, issue 1, pp. 1 - 16
(Article)
Abstract
Tumor immunosurveillance plays a major role in melanoma, prompting the development of immunotherapy strategies. The gut microbiota composition, influencing peripheral and tumoral immune tonus, earned its credentials among predictors of survival in melanoma. The MIND-DC phase III trial (NCT02993315) randomized (2:1 ratio) 148 patients with stage IIIB/C melanoma to adjuvant
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treatment with autologous natural dendritic cell (nDC) or placebo (PL). Overall, 144 patients collected serum and stool samples before and after 2 bimonthly injections to perform metabolomics (MB) and metagenomics (MG) as prespecified exploratory analysis. Clinical outcomes are reported separately. Here we show that different microbes were associated with prognosis, with the health-related Faecalibacterium prausnitzii standing out as the main beneficial taxon for no recurrence at 2 years (p = 0.008 at baseline, nDC arm). Therapy coincided with major MB perturbations (acylcarnitines, carboxylic and fatty acids). Despite randomization, nDC arm exhibited MG and MB bias at baseline: relative under-representation of F. prausnitzii, and perturbations of primary biliary acids (BA). F. prausnitzii anticorrelated with BA, medium- and long-chain acylcarnitines. Combined, these MG and MB biomarkers markedly determined prognosis. Altogether, the host-microbial interaction may play a role in localized melanoma. We value systematic MG and MB profiling in randomized trials to avoid baseline differences attributed to host-microbe interactions.
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Keywords: General Chemistry, General Biochemistry,Genetics and Molecular Biology, General Physics and Astronomy
ISSN: 2041-1723
Publisher: Nature Publishing Group
Note: Publisher Copyright: © The Author(s) 2024.
(Peer reviewed)