5 results on '"Jean-Eudes Fahrner"'
Search Results
2. Metabolomic analyses of COVID-19 patients unravel stage-dependent and prognostic biomarkers
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François-Xavier Danlos, Claudia Grajeda-Iglesias, Sylvère Durand, Allan Sauvat, Mathilde Roumier, Delphine Cantin, Emeline Colomba, Julien Rohmer, Fanny Pommeret, Giulia Baciarello, Christophe Willekens, Marc Vasse, Frank Griscelli, Jean-Eudes Fahrner, Anne-Gaëlle Goubet, Agathe Dubuisson, Lisa Derosa, Nitharsshini Nirmalathasan, Delphine Bredel, Séverine Mouraud, Caroline Pradon, Annabelle Stoclin, Flore Rozenberg, Jérôme Duchemin, Georges Jourdi, Syrine Ellouze, Françoise Levavasseur, Laurence Albigès, Jean-Charles Soria, Fabrice Barlesi, Eric Solary, Fabrice André, Frédéric Pène, Félix Ackerman, Luc Mouthon, Laurence Zitvogel, Aurélien Marabelle, Jean-Marie Michot, Michaela Fontenay, and Guido Kroemer
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Cytology ,QH573-671 - Abstract
Abstract The circulating metabolome provides a snapshot of the physiological state of the organism responding to pathogenic challenges. Here we report alterations in the plasma metabolome reflecting the clinical presentation of COVID-19 patients with mild (ambulatory) diseases, moderate disease (radiologically confirmed pneumonitis, hospitalization and oxygen therapy), and critical disease (in intensive care). This analysis revealed major disease- and stage-associated shifts in the metabolome, meaning that at least 77 metabolites including amino acids, lipids, polyamines and sugars, as well as their derivatives, were altered in critical COVID-19 patient’s plasma as compared to mild COVID-19 patients. Among a uniformly moderate cohort of patients who received tocilizumab, only 10 metabolites were different among individuals with a favorable evolution as compared to those who required transfer into the intensive care unit. The elevation of one single metabolite, anthranilic acid, had a poor prognostic value, correlating with the maintenance of high interleukin-10 and -18 levels. Given that products of the kynurenine pathway including anthranilic acid have immunosuppressive properties, we speculate on the therapeutic utility to inhibit the rate-limiting enzymes of this pathway including indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase.
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- 2021
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3. Immune system and intestinal microbiota determine efficacy of androgen deprivation therapy against prostate cancer
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Hang Phuong Pham, Douglas G McNeel, Laurence Zitvogel, Corentin Richard, Antoine Toubert, Guido Kroemer, Stéphane Culine, Karim Fizazi, Bertrand Routy, Lisa Derosa, Francesco Asnicar, Nicola Segata, Gladys Ferrere, Florent Ginhoux, Anne-Gaelle Goubet, Safae Terrisse, Kousuke Ueda, Andrew Maltez Thomas, Valentin Quiniou, Cassandra Thelemaque, Garett Dunsmore, Emmanuel Clave, Melissa Gamat-Huber, Satoru Yonekura, Conrad Rauber, Jean-Eudes Fahrner, Eugenie Pizzato, Pierre Ly, Marine Fidelle, Marine Mazzenga, Carolina Alves Costa Silva, Federica Armanini, Federica Pinto, Romain Daillère, Pierre Blanchard, Paule Opolon, and Aymeric Silvin
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background Prostate cancer (PC) responds to androgen deprivation therapy (ADT) usually in a transient fashion, progressing from hormone-sensitive PC (HSPC) to castration-resistant PC (CRPC). We investigated a mouse model of PC as well as specimens from PC patients to unravel an unsuspected contribution of thymus-derived T lymphocytes and the intestinal microbiota in the efficacy of ADT.Methods Preclinical experiments were performed in PC-bearing mice, immunocompetent or immunodeficient. In parallel, we prospectively included 65 HSPC and CRPC patients (Oncobiotic trial) to analyze their feces and blood specimens.Results In PC-bearing mice, ADT increased thymic cellularity and output. PC implanted in T lymphocyte-depleted or athymic mice responded less efficiently to ADT than in immunocompetent mice. Moreover, depletion of the intestinal microbiota by oral antibiotics reduced the efficacy of ADT. PC reduced the relative abundance of Akkermansia muciniphila in the gut, and this effect was reversed by ADT. Moreover, cohousing of PC-bearing mice with tumor-free mice or oral gavage with Akkermansia improved the efficacy of ADT. This appears to be applicable to PC patients because long-term ADT resulted in an increase of thymic output, as demonstrated by an increase in circulating recent thymic emigrant cells (sjTRECs). Moreover, as compared with HSPC controls, CRPC patients demonstrated a shift in their intestinal microbiota that significantly correlated with sjTRECs. While feces from healthy volunteers restored ADT efficacy, feces from PC patients failed to do so.Conclusions These findings suggest the potential clinical utility of reversing intestinal dysbiosis and repairing acquired immune defects in PC patients.
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- 2022
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4. Immunodynamics of explanted human tumors for immuno‐oncology
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Agathe Dubuisson, Jean‐Eudes Fahrner, Anne‐Gaëlle Goubet, Safae Terrisse, Nicolas Voisin, Charles Bayard, Sebastien Lofek, Damien Drubay, Delphine Bredel, Séverine Mouraud, Sandrine Susini, Alexandria Cogdill, Lucas Rebuffet, Elise Ballot, Nicolas Jacquelot, Vincent Thomas de Montpreville, Odile Casiraghi, Camélia Radulescu, Sophie Ferlicot, David J Figueroa, Sapna Yadavilli, Jeremy D Waight, Marc Ballas, Axel Hoos, Thomas Condamine, Bastien Parier, Christophe Gaudillat, Bertrand Routy, François Ghiringhelli, Lisa Derosa, Ingrid Breuskin, Mathieu Rouanne, Fabrice André, Cédric Lebacle, Hervé Baumert, Marie Wislez, Elie Fadel, Isabelle Cremer, Laurence Albiges, Birgit Geoerger, Jean‐Yves Scoazec, Yohann Loriot, Guido Kroemer, Aurélien Marabelle, Mélodie Bonvalet, and Laurence Zitvogel
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“in sitro” assay ,cancer ,immune checkpoint inhibitors ,immunomonitoring ,precision oncology ,Medicine (General) ,R5-920 ,Genetics ,QH426-470 - Abstract
Abstract Decision making in immuno‐oncology is pivotal to adapt therapy to the tumor microenvironment (TME) of the patient among the numerous options of monoclonal antibodies or small molecules. Predicting the best combinatorial regimen remains an unmet medical need. Here, we report a multiplex functional and dynamic immuno‐assay based on the capacity of the TME to respond to ex vivo stimulation with twelve immunomodulators including immune checkpoint inhibitors (ICI) in 43 human primary tumors. This "in sitro" (in situ/in vitro) assay has the potential to predict unresponsiveness to anti‐PD‐1 mAbs, and to detect the most appropriate and personalized combinatorial regimen. Prospective clinical trials are awaited to validate this in sitro assay.
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- 2021
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5. Trial Watch: Oncolytic viro-immunotherapy of hematologic and solid tumors
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Jonathan G. Pol, Sarah Lévesque, Samuel T. Workenhe, Shashi Gujar, Fabrice Le Boeuf, Derek R. Clements, Jean-Eudes Fahrner, Laetitia Fend, John C. Bell, Karen L. Mossman, Jitka Fucikova, Radek Spisek, Laurence Zitvogel, Guido Kroemer, and Lorenzo Galluzzi
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cavatak ,dnx-2401 ,hf10 ,maraba mg1 ,mv-nis ,pexa-vec ,reolysin ,t-vec ,Immunologic diseases. Allergy ,RC581-607 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Oncolytic viruses selectively target and kill cancer cells in an immunogenic fashion, thus supporting the establishment of therapeutically relevant tumor-specific immune responses. In 2015, the US Food and Drug Administration (FDA) approved the oncolytic herpes simplex virus T-VEC for use in advanced melanoma patients. Since then, a plethora of trials has been initiated to assess the safety and efficacy of multiple oncolytic viruses in patients affected with various malignancies. Here, we summarize recent preclinical and clinical progress in the field of oncolytic virotherapy.
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- 2018
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