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

Autor: Alves Costa Silva C; Gustave Roussy Cancer Campus (GRCC), ClinicObiome, Villejuif Cedex, France.; Faculté de Médecine, Université Paris-Saclay, Kremlin-Bicêtre, France.; Institut National de la Santé Et de la Recherche Médicale (INSERM) U1015, Équipe Labellisée - Ligue Nationale contre le Cancer, Villejuif, France., Piccinno G; Department of Computational, Cellular and Integrative Biology (CIBIO), University of Trento, Trento, Italy., Suissa D; Gustave Roussy Cancer Campus (GRCC), ClinicObiome, Villejuif Cedex, France.; Faculté de Médecine, Université Paris-Saclay, Kremlin-Bicêtre, France.; Institut National de la Santé Et de la Recherche Médicale (INSERM) U1015, Équipe Labellisée - Ligue Nationale contre le Cancer, Villejuif, France., Bourgin M; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France.; Centre de Recherche des Cordeliers, INSERM U1138, Équipe Labellisée - Ligue Nationale contre le Cancer, Université Paris Cité, Sorbonne Université, Paris, France., Schreibelt G; Medical BioSciences, Radboud Institute for Medical Innovation, Radboud university medical center, Nijmegen, The Netherlands., Durand S; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France.; Centre de Recherche des Cordeliers, INSERM U1138, Équipe Labellisée - Ligue Nationale contre le Cancer, Université Paris Cité, Sorbonne Université, Paris, France., Birebent R; Gustave Roussy Cancer Campus (GRCC), ClinicObiome, Villejuif Cedex, France.; Faculté de Médecine, Université Paris-Saclay, Kremlin-Bicêtre, France.; Institut National de la Santé Et de la Recherche Médicale (INSERM) U1015, Équipe Labellisée - Ligue Nationale contre le Cancer, Villejuif, France., Fidelle M; Gustave Roussy Cancer Campus (GRCC), ClinicObiome, Villejuif Cedex, France.; Institut National de la Santé Et de la Recherche Médicale (INSERM) U1015, Équipe Labellisée - Ligue Nationale contre le Cancer, Villejuif, France., Sow C; Gustave Roussy Cancer Campus (GRCC), ClinicObiome, Villejuif Cedex, France.; Institut National de la Santé Et de la Recherche Médicale (INSERM) U1015, Équipe Labellisée - Ligue Nationale contre le Cancer, Villejuif, France., Aprahamian F; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France.; Centre de Recherche des Cordeliers, INSERM U1138, Équipe Labellisée - Ligue Nationale contre le Cancer, Université Paris Cité, Sorbonne Université, Paris, France., Manghi P; Department of Computational, Cellular and Integrative Biology (CIBIO), University of Trento, Trento, Italy., Punčochář M; Department of Computational, Cellular and Integrative Biology (CIBIO), University of Trento, Trento, Italy., Asnicar F; Department of Computational, Cellular and Integrative Biology (CIBIO), University of Trento, Trento, Italy., Pinto F; Department of Computational, Cellular and Integrative Biology (CIBIO), University of Trento, Trento, Italy., Armanini F; Department of Computational, Cellular and Integrative Biology (CIBIO), University of Trento, Trento, Italy., Terrisse S; Oncology Department, Assistance Publique Hôpitaux de Paris (AP-HP), Hôpital Saint-Louis, Paris, France., Routy B; Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada.; Hematology-Oncology Division, Department of Medicine, Centre Hospitalier de l'Université de Montréal (CHUM), Montréal, QC, Canada., Drubay D; Gustave Roussy Cancer Campus (GRCC), ClinicObiome, Villejuif Cedex, France.; Office of Biostatistics and Epidemiology, Gustave Roussy Cancer Campus, Université Paris-Saclay, Villejuif, France.; Inserm, Université Paris-Saclay, CESP U1018, Oncostat, labeled Ligue Contre le Cancer, Villejuif, France., Eggermont AMM; Princess Máxima Center and University Medical Center Utrecht, 3584 CS Utrecht, The Netherlands.; Comprehensive Cancer Center Munich, Technical University Munich & Ludwig Maximiliaan University, Munich, Germany., Kroemer G; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France.; Centre de Recherche des Cordeliers, INSERM U1138, Équipe Labellisée - Ligue Nationale contre le Cancer, Université Paris Cité, Sorbonne Université, Paris, France.; Department of Biology, Institut du Cancer Paris CARPEM, Hôpital Européen Georges Pompidou, AP-HP, Paris, France., Segata N; Department of Computational, Cellular and Integrative Biology (CIBIO), University of Trento, Trento, Italy.; Department of Experimental Oncology, IEO European Institute of Oncology IRCCS, Milan, Italy., Zitvogel L; Gustave Roussy Cancer Campus (GRCC), ClinicObiome, Villejuif Cedex, France. laurence.zitvogel@gustaveroussy.fr.; Faculté de Médecine, Université Paris-Saclay, Kremlin-Bicêtre, France. laurence.zitvogel@gustaveroussy.fr.; Institut National de la Santé Et de la Recherche Médicale (INSERM) U1015, Équipe Labellisée - Ligue Nationale contre le Cancer, Villejuif, France. laurence.zitvogel@gustaveroussy.fr.; Center of Clinical Investigations BIOTHERIS, INSERM CIC1428, Villejuif, France. laurence.zitvogel@gustaveroussy.fr., Derosa L; Gustave Roussy Cancer Campus (GRCC), ClinicObiome, Villejuif Cedex, France.; Faculté de Médecine, Université Paris-Saclay, Kremlin-Bicêtre, France.; Institut National de la Santé Et de la Recherche Médicale (INSERM) U1015, Équipe Labellisée - Ligue Nationale contre le Cancer, Villejuif, France., Bol KF; Medical BioSciences, Radboud Institute for Medical Innovation, Radboud university medical center, Nijmegen, The Netherlands.; Department of Medical Oncology, Radboud university medical center, Nijmegen, The Netherlands., de Vries IJM; Medical BioSciences, Radboud Institute for Medical Innovation, Radboud university medical center, Nijmegen, The Netherlands.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Feb 23; Vol. 15 (1), pp. 1633. Date of Electronic Publication: 2024 Feb 23.
DOI: 10.1038/s41467-024-45357-1
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz: