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

Author

Listed:
  • Carolina Alves Costa Silva

    (ClinicObiome
    Université Paris-Saclay
    Équipe Labellisée – Ligue Nationale contre le Cancer)

  • Gianmarco Piccinno

    (University of Trento)

  • Déborah Suissa

    (ClinicObiome
    Université Paris-Saclay
    Équipe Labellisée – Ligue Nationale contre le Cancer)

  • Mélanie Bourgin

    (Gustave Roussy Cancer Campus
    Université Paris Cité, Sorbonne Université)

  • Gerty Schreibelt

    (Radboud university medical center)

  • Sylvère Durand

    (Gustave Roussy Cancer Campus
    Université Paris Cité, Sorbonne Université)

  • Roxanne Birebent

    (ClinicObiome
    Université Paris-Saclay
    Équipe Labellisée – Ligue Nationale contre le Cancer)

  • Marine Fidelle

    (ClinicObiome
    Équipe Labellisée – Ligue Nationale contre le Cancer)

  • Cissé Sow

    (ClinicObiome
    Équipe Labellisée – Ligue Nationale contre le Cancer)

  • Fanny Aprahamian

    (Gustave Roussy Cancer Campus
    Université Paris Cité, Sorbonne Université)

  • 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)
    Centre Hospitalier de l’Université de Montréal (CHUM))

  • Damien Drubay

    (ClinicObiome
    Université Paris-Saclay
    Inserm, Université Paris-Saclay, CESP U1018, Oncostat, labeled Ligue Contre le Cancer)

  • Alexander M. M. Eggermont

    (Princess Máxima Center and University Medical Center Utrecht
    Technical University Munich & Ludwig Maximiliaan University)

  • Guido Kroemer

    (Gustave Roussy Cancer Campus
    Université Paris Cité, Sorbonne Université
    Hôpital Européen Georges Pompidou, AP-HP)

  • Nicola Segata

    (University of Trento
    IEO European Institute of Oncology IRCCS)

  • Laurence Zitvogel

    (ClinicObiome
    Université Paris-Saclay
    Équipe Labellisée – Ligue Nationale contre le Cancer
    Center of Clinical Investigations BIOTHERIS)

  • Lisa Derosa

    (ClinicObiome
    Université Paris-Saclay
    Équipe Labellisée – Ligue Nationale contre le Cancer)

  • Kalijn F. Bol

    (Radboud university medical center
    Radboud university medical center)

  • I. Jolanda M. Vries

    (Radboud university medical center)

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.

Suggested Citation

  • Carolina Alves Costa Silva & Gianmarco Piccinno & Déborah Suissa & Mélanie Bourgin & Gerty Schreibelt & Sylvère Durand & Roxanne Birebent & Marine Fidelle & Cissé Sow & Fanny Aprahamian & Paolo Manghi, 2024. "Influence of microbiota-associated metabolic reprogramming on clinical outcome in patients with melanoma from the randomized adjuvant dendritic cell-based MIND-DC trial," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45357-1
    DOI: 10.1038/s41467-024-45357-1
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