Influence of microbiota-associated metabolic reprogramming on clinical outcome in patients with melanoma from the randomized adjuvant dendritic cell-based MIND-DC trial

Carolina Alves Costa Silva, Gianmarco Piccinno, Déborah Suissa, Mélanie Bourgin, Gerty Schreibelt, Sylvère Durand, Roxanne Birebent, Marine Fidelle, Cissé Sow, Fanny Aprahamian, Paolo Manghi, Michal Punčochář, Francesco Asnicar, Federica Pinto, Federica Armanini, Safae Terrisse, Bertrand Routy, Damien Drubay, Alexander M. M. Eggermont, Guido Kroemer, Nicola Segata, Laurence Zitvogel (), Lisa Derosa, Kalijn F. Bol and I. Jolanda M. Vries
Additional contact information
Carolina Alves Costa Silva: ClinicObiome
Gianmarco Piccinno: University of Trento
Déborah Suissa: ClinicObiome
Mélanie Bourgin: Gustave Roussy Cancer Campus
Gerty Schreibelt: Radboud university medical center
Sylvère Durand: Gustave Roussy Cancer Campus
Roxanne Birebent: ClinicObiome
Marine Fidelle: ClinicObiome
Cissé Sow: ClinicObiome
Fanny Aprahamian: Gustave Roussy Cancer Campus
Paolo Manghi: University of Trento
Michal Punčochář: University of Trento
Francesco Asnicar: University of Trento
Federica Pinto: University of Trento
Federica Armanini: University of Trento
Safae Terrisse: Assistance Publique Hôpitaux de Paris (AP-HP)
Bertrand Routy: Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM)
Damien Drubay: ClinicObiome
Alexander M. M. Eggermont: Princess Máxima Center and University Medical Center Utrecht
Guido Kroemer: Gustave Roussy Cancer Campus
Nicola Segata: University of Trento
Laurence Zitvogel: ClinicObiome
Lisa Derosa: ClinicObiome
Kalijn F. Bol: Radboud university medical center
I. Jolanda M. Vries: Radboud university medical center

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: 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 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.

Date: 2024
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DOI: 10.1038/s41467-024-45357-1

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