The MIND-DC trial in patients with advanced melanoma showed that adjuvant natural DC (nDC) therapy induced Ag-specific immune responses, but did not provide a survival benefit. Digging deeper, Silva, et al. reported that despite randomization, there was a significant bias at baseline in serum metabolomics and fecal metagenomics that correlated with prognosis. At baseline, the nDC arm had significantly fewer commensals, such as Faecalibacterium prausnitzii, that highly correlated with 2-year RFS, as well as perturbations of primary biliary acids and lipids, suggesting host-microbial interactions influenced the nDC treatment response.
Contributed by Katherine Turner
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.
Author Info: (1) Gustave Roussy Cancer Campus (GRCC), ClinicObiome, Villejuif Cedex, France. Facult de Mdecine, Universit Paris-Saclay, Kremlin-Bictre, France. Institut National de la Sant
Author Info: (1) Gustave Roussy Cancer Campus (GRCC), ClinicObiome, Villejuif Cedex, France. Facult de Mdecine, Universit Paris-Saclay, Kremlin-Bictre, France. Institut National de la Sant Et de la Recherche Mdicale (INSERM) U1015, quipe Labellise - Ligue Nationale contre le Cancer, Villejuif, France. (2) Department of Computational, Cellular and Integrative Biology (CIBIO), University of Trento, Trento, Italy. (3) Gustave Roussy Cancer Campus (GRCC), ClinicObiome, Villejuif Cedex, France. Facult de Mdecine, Universit Paris-Saclay, Kremlin-Bictre, France. Institut National de la Sant Et de la Recherche Mdicale (INSERM) U1015, quipe Labellise - Ligue Nationale contre le Cancer, Villejuif, France. (4) Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France. Centre de Recherche des Cordeliers, INSERM U1138, quipe Labellise - Ligue Nationale contre le Cancer, Universit Paris Cit, Sorbonne Universit, Paris, France. (5) Medical BioSciences, Radboud Institute for Medical Innovation, Radboud university medical center, Nijmegen, The Netherlands. (6) Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France. Centre de Recherche des Cordeliers, INSERM U1138, quipe Labellise - Ligue Nationale contre le Cancer, Universit Paris Cit, Sorbonne Universit, Paris, France. (7) Gustave Roussy Cancer Campus (GRCC), ClinicObiome, Villejuif Cedex, France. Facult de Mdecine, Universit Paris-Saclay, Kremlin-Bictre, France. Institut National de la Sant Et de la Recherche Mdicale (INSERM) U1015, quipe Labellise - Ligue Nationale contre le Cancer, Villejuif, France. (8) Gustave Roussy Cancer Campus (GRCC), ClinicObiome, Villejuif Cedex, France. Institut National de la Sant Et de la Recherche Mdicale (INSERM) U1015, quipe Labellise - Ligue Nationale contre le Cancer, Villejuif, France. (9) Gustave Roussy Cancer Campus (GRCC), ClinicObiome, Villejuif Cedex, France. Institut National de la Sant Et de la Recherche Mdicale (INSERM) U1015, quipe Labellise - Ligue Nationale contre le Cancer, Villejuif, France. (10) Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France. Centre de Recherche des Cordeliers, INSERM U1138, quipe Labellise - Ligue Nationale contre le Cancer, Universit Paris Cit, Sorbonne Universit, Paris, France. (11) Department of Computational, Cellular and Integrative Biology (CIBIO), University of Trento, Trento, Italy. (12) Department of Computational, Cellular and Integrative Biology (CIBIO), University of Trento, Trento, Italy. (13) Department of Computational, Cellular and Integrative Biology (CIBIO), University of Trento, Trento, Italy. (14) Department of Computational, Cellular and Integrative Biology (CIBIO), University of Trento, Trento, Italy. (15) Department of Computational, Cellular and Integrative Biology (CIBIO), University of Trento, Trento, Italy. (16) Oncology Department, Assistance Publique Hpitaux de Paris (AP-HP), Hpital Saint-Louis, Paris, France. (17) Centre de Recherche du Centre Hospitalier de l'Universit de Montral (CRCHUM), Montral, QC, Canada. Hematology-Oncology Division, Department of Medicine, Centre Hospitalier de l'Universit de Montral (CHUM), Montral, QC, Canada. (18) Gustave Roussy Cancer Campus (GRCC), ClinicObiome, Villejuif Cedex, France. Office of Biostatistics and Epidemiology, Gustave Roussy Cancer Campus, Universit Paris-Saclay, Villejuif, France. Inserm, Universit Paris-Saclay, CESP U1018, Oncostat, labeled Ligue Contre le Cancer, Villejuif, France. (19) Princess Mxima Center and University Medical Center Utrecht, 3584 CS Utrecht, The Netherlands. Comprehensive Cancer Center Munich, Technical University Munich & Ludwig Maximiliaan University, Munich, Germany. (20) Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France. Centre de Recherche des Cordeliers, INSERM U1138, quipe Labellise - Ligue Nationale contre le Cancer, Universit Paris Cit, Sorbonne Universit, Paris, France. Department of Biology, Institut du Cancer Paris CARPEM, Hpital Europen Georges Pompidou, AP-HP, Paris, France. (21) 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. (22) Gustave Roussy Cancer Campus (GRCC), ClinicObiome, Villejuif Cedex, France. laurence.zitvogel@gustaveroussy.fr. Facult de Mdecine, Universit Paris-Saclay, Kremlin-Bictre, France. laurence.zitvogel@gustaveroussy.fr. Institut National de la Sant Et de la Recherche Mdicale (INSERM) U1015, quipe Labellise - Ligue Nationale contre le Cancer, Villejuif, France. laurence.zitvogel@gustaveroussy.fr. Center of Clinical Investigations BIOTHERIS, INSERM CIC1428, Villejuif, France. laurence.zitvogel@gustaveroussy.fr. (23) Gustave Roussy Cancer Campus (GRCC), ClinicObiome, Villejuif Cedex, France. Facult de Mdecine, Universit Paris-Saclay, Kremlin-Bictre, France. Institut National de la Sant Et de la Recherche Mdicale (INSERM) U1015, quipe Labellise - Ligue Nationale contre le Cancer, Villejuif, France. (24) 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. (25) Medical BioSciences, Radboud Institute for Medical Innovation, Radboud university medical center, Nijmegen, The Netherlands.
