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1. Correction: Metabolomic analyses of COVID-19 patients unravel stage-dependent and prognostic biomarkers

Author

Danlos, François-Xavier, Grajeda-Iglesias, Claudia, Durand, Sylvère, Sauvat, Allan, Roumier, Mathilde, Cantin, Delphine, Colomba, Emeline, Rohmer, Julien, Pommeret, Fanny, Baciarello, Giulia, Willekens, Christophe, Vasse, Marc, Griscelli, Frank, Fahrner, Jean-Eudes, Goubet, Anne-Gaëlle, Dubuisson, Agathe, Derosa, Lisa, Nirmalathasan, Nitharsshini, Bredel, Delphine, Mouraud, Séverine, Pradon, Caroline, Stoclin, Annabelle, Rozenberg, Flore, Duchemin, Jérôme, Jourdi, Georges, Ellouze, Syrine, Levavasseur, Françoise, Albigès, Laurence, Soria, Jean-Charles, Barlesi, Fabrice, Solary, Eric, André, Fabrice, Pène, Frédéric, Ackerman, Félix, Mouthon, Luc, Zitvogel, Laurence, Marabelle, Aurélien, Michot, Jean-Marie, Fontenay, Michaela, and Kroemer, Guido

Published
2024
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2. Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer

Author

Derosa, Lisa, Routy, Bertrand, Thomas, Andrew Maltez, Iebba, Valerio, Zalcman, Gerard, Friard, Sylvie, Mazieres, Julien, Audigier-Valette, Clarisse, Moro-Sibilot, Denis, Goldwasser, François, Silva, Carolina Alves Costa, Terrisse, Safae, Bonvalet, Melodie, Scherpereel, Arnaud, Pegliasco, Hervé, Richard, Corentin, Ghiringhelli, François, Elkrief, Arielle, Desilets, Antoine, Blanc-Durand, Felix, Cumbo, Fabio, Blanco, Aitor, Boidot, Romain, Chevrier, Sandy, Daillère, Romain, Kroemer, Guido, Alla, Laurie, Pons, Nicolas, Le Chatelier, Emmanuelle, Galleron, Nathalie, Roume, Hugo, Dubuisson, Agathe, Bouchard, Nicole, Messaoudene, Meriem, Drubay, Damien, Deutsch, Eric, Barlesi, Fabrice, Planchard, David, Segata, Nicola, Martinez, Stéphanie, Zitvogel, Laurence, Soria, Jean-Charles, and Besse, Benjamin

Published
2022
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3. Prolonged SARS-CoV-2 RNA virus shedding and lymphopenia are hallmarks of COVID-19 in cancer patients with poor prognosis

Author

Goubet, Anne-Gaëlle, Dubuisson, Agathe, Geraud, Arthur, Danlos, François-Xavier, Terrisse, Safae, Silva, Carolina Alves Costa, Drubay, Damien, Touri, Lea, Picard, Marion, Mazzenga, Marine, Silvin, Aymeric, Dunsmore, Garett, Haddad, Yacine, Pizzato, Eugenie, Ly, Pierre, Flament, Caroline, Melenotte, Cléa, Solary, Eric, Fontenay, Michaela, Garcia, Gabriel, Balleyguier, Corinne, Lassau, Nathalie, Maeurer, Markus, Grajeda-Iglesias, Claudia, Nirmalathasan, Nitharsshini, Aprahamian, Fanny, Durand, Sylvère, Kepp, Oliver, Ferrere, Gladys, Thelemaque, Cassandra, Lahmar, Imran, Fahrner, Jean-Eudes, Meziani, Lydia, Ahmed-Belkacem, Abdelhakim, Saïdani, Nadia, La Scola, Bernard, Raoult, Didier, Gentile, Stéphanie, Cortaredona, Sébastien, Ippolito, Giuseppe, Lelouvier, Benjamin, Roulet, Alain, Andre, Fabrice, Barlesi, Fabrice, Soria, Jean-Charles, Pradon, Caroline, Gallois, Emmanuelle, Pommeret, Fanny, Colomba, Emeline, Ginhoux, Florent, Kazandjian, Suzanne, Elkrief, Arielle, Routy, Bertrand, Miyara, Makoto, Gorochov, Guy, Deutsch, Eric, Albiges, Laurence, Stoclin, Annabelle, Gachot, Bertrand, Florin, Anne, Merad, Mansouria, Scotte, Florian, Assaad, Souad, Kroemer, Guido, Blay, Jean-Yves, Marabelle, Aurélien, Griscelli, Frank, Zitvogel, Laurence, and Derosa, Lisa

Published
2021
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4. Metabolomic analyses of COVID-19 patients unravel stage-dependent and prognostic biomarkers

Author

Danlos, François-Xavier, Grajeda-Iglesias, Claudia, Durand, Sylvère, Sauvat, Allan, Roumier, Mathilde, Cantin, Delphine, Colomba, Emeline, Rohmer, Julien, Pommeret, Fanny, Baciarello, Giulia, Willekens, Christophe, Vasse, Marc, Griscelli, Frank, Fahrner, Jean-Eudes, Goubet, Anne-Gaëlle, Dubuisson, Agathe, Derosa, Lisa, Nirmalathasan, Nitharsshini, Bredel, Delphine, Mouraud, Séverine, Pradon, Caroline, Stoclin, Annabelle, Rozenberg, Flore, Duchemin, Jérôme, Jourdi, Georges, Ellouze, Syrine, Levavasseur, Françoise, Albigès, Laurence, Soria, Jean-Charles, Barlesi, Fabrice, Solary, Eric, André, Fabrice, Pène, Frédéric, Ackerman, Félix, Mouthon, Luc, Zitvogel, Laurence, Marabelle, Aurélien, Michot, Jean-Marie, Fontenay, Michaela, and Kroemer, Guido

Published
2021
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5. Immunodynamics of explanted human tumors for immuno‐oncology

Author

Dubuisson, Agathe, Fahrner, Jean‐Eudes, Goubet, Anne‐Gaëlle, Terrisse, Safae, Voisin, Nicolas, Bayard, Charles, Lofek, Sebastien, Drubay, Damien, Bredel, Delphine, Mouraud, Séverine, Susini, Sandrine, Cogdill, Alexandria, Rebuffet, Lucas, Ballot, Elise, Jacquelot, Nicolas, Thomas de Montpreville, Vincent, Casiraghi, Odile, Radulescu, Camélia, Ferlicot, Sophie, Figueroa, David J, Yadavilli, Sapna, Waight, Jeremy D, Ballas, Marc, Hoos, Axel, Condamine, Thomas, Parier, Bastien, Gaudillat, Christophe, Routy, Bertrand, Ghiringhelli, François, Derosa, Lisa, Breuskin, Ingrid, Rouanne, Mathieu, André, Fabrice, Lebacle, Cédric, Baumert, Hervé, Wislez, Marie, Fadel, Elie, Cremer, Isabelle, Albiges, Laurence, Geoerger, Birgit, Scoazec, Jean‐Yves, Loriot, Yohann, Kroemer, Guido, Marabelle, Aurélien, Bonvalet, Mélodie, and Zitvogel, Laurence

Published
2021
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6. Characterization of CD4+ and CD8+ T cells responses in the mixed lymphocyte reaction by flow cytometry and single cell RNA sequencing.

Author

Mangelinck, Adèle, Dubuisson, Agathe, Becht, Etienne, Dromaint-Catesson, Sandra, Fasquel, Manon, Provost, Nicolas, Walas, Dawid, Darville, Hélène, Galizzi, Jean-Pierre, Lefebvre, Céline, Blanc, Véronique, and Lombardi, Vincent

Subjects
T cells, RNA sequencing, FLOW cytometry, LYMPHOCYTES, CELL physiology
Abstract

Background: The Mixed Lymphocyte Reaction (MLR) consists in the allogeneic co-culture of monocytes derived dendritic cells (MoDCs) with T cells fromanother donor. This in vitro assay is largely used for the assessment of immunotherapy compounds. Nevertheless, the phenotypic changes associated with lymphocyte responsiveness under MLR have never been thoroughly evaluated. Methods: Here, we used multiplex cytokine and chemokine assays, multiparametric flow cytometry and single cell RNA sequencing to deeply characterize T cells activation and function in the context of CD4+- and CD8+-specific MLR kinetics. Results: We showed that CD4+ and CD8+ T cells in MLR share common classical markers of response such as polyfunctionality, increased proliferation and CD25 expression but differ in their kinetics and amplitude of activation as well as their patterns of cytokines secretion and immune checkpoints expression. The analysis of immunoreactive Ki-67+CD25+ T cells identified PBK, LRR1 and MYO1G as new potential markers of MLR response. Using cell-cell communication network inference and pathway analysis on single cell RNA sequencing data, we also highlighted key components of the immunological synapse occurring between T cells and the stimulatory MoDCs together with downstream signaling pathways involved in CD4+ and CD8+ T cells activation. Conclusion: These results provide a deep understanding of the kinetics of the MLR assay for CD4+ or CD8+ T cells and may allow to better characterize compounds impacting MLR and eventually identify new strategies for immunotherapy in cancer. [ABSTRACT FROM AUTHOR]

Published
2024
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8. Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in advanced non-small cell lung cancer patients

Author

Derosa, Lisa, Routy, Bertrand, Thomas, Andrew Maltez, Iebba, Valerio, Zalcman, Gerard, Friard, Sylvie, Mazieres, Julien, Audigier-Valette, Clarisse, Moro-Sibilot, Denis, Goldwasser, François, Silva, Carolina Alves Costa, Terrisse, Safae, Bonvalet, Melodie, Scherpereel, Arnaud, Pegliasco, Hervé, Richard, Corentin, Ghiringhelli, François, Elkrief, Arielle, Desilets, Antoine, Blanc-Durand, Felix, Cumbo, Fabio, Blanco, Aitor, Boidot, Romain, Chevrier, Sandy, Daillère, Romain, Kroemer, Guido, Alla, Laurie, Pons, Nicolas, Chatelier, Emmanuelle Le, Galleron, Nathalie, Roume, Hugo, Dubuisson, Agathe, Bouchard, Nicole, Messaoudene, Meriem, Drubay, Damien, Deutsch, Eric, Barlesi, Fabrice, Planchard, David, Segata, Nicola, Martinez, Stéphanie, Zitvogel, Laurence, Soria, Jean-Charles, and Besse, Benjamin

Subjects
Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Humans, Immunologic Factors, Akkermansia, Immunotherapy, Article
Abstract

Aside from PD-L1 expression, biomarkers of response to immune checkpoint inhibitors (ICI) in non-small cell lung cancer (NSCLC) are needed. We previously reported in 100 NSCLC and kidney cancer patients that fecal Akkermansia muciniphila (Akk) correlated with ICI clinical success. The endpoint of this study was to prospectively validate the prognostic significance of fecal Akk in advanced NSCLC patients treated with first or second line ICI. We performed shotgun metagenomics-based microbiome profiling using two different pipelines in 338 NSCLC patients. Baseline stool Akk was associated with increased objective response rates and overall survival in multivariate analyses, independent of PD-L1 expression, antibiotics and performance status. Intestinal Akk was accompanied by a richer commensalism, including Eubacterium hallii and Bifidobacterium adolescentis and a more inflamed tumor microenvironment in a subset of patients. However, antibiotic use (20% of cases) coincided with a relative dominance of Akk above 4.8% accompanied with the genus Clostridium, both associated with resistance to ICI. Our study shows significant differences in relative abundance of Akk that could be useful for future studies as a tool to aid patient stratification.

Published
2022

9. Circulating acetylated polyamines correlate with Covid-19 severity in cancer patients

Author

Bourgin, Mélanie, primary, Derosa, Lisa, additional, Silva, Carolina Alves Costa, additional, Goubet, Anne-Gaëlle, additional, Dubuisson, Agathe, additional, Danlos, François-Xavier, additional, Grajeda-Iglesias, Claudia, additional, Cerbone, Luigi, additional, Geraud, Arthur, additional, Laparra, Ariane, additional, Aprahamian, Fanny, additional, Nirmalathasan, Nitharsshini, additional, Madeo, Frank, additional, Zitvogel, Laurence, additional, Kroemer, Guido, additional, and Durand, Sylvère, additional

Published
2021
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10. Cross-tissue single-cell landscape of human monocytes and macrophages in health and disease

Author

Mulder, Kevin, primary, Patel, Amit Ashok, additional, Kong, Wan Ting, additional, Piot, Cécile, additional, Halitzki, Evelyn, additional, Dunsmore, Garett, additional, Khalilnezhad, Shabnam, additional, Irac, Sergio Erdal, additional, Dubuisson, Agathe, additional, Chevrier, Marion, additional, Zhang, Xiao Meng, additional, Tam, John Kit Chung, additional, Lim, Tony Kiat Hon, additional, Wong, Regina Men Men, additional, Pai, Rhea, additional, Khalil, Ahmed Ibrahim Samir, additional, Chow, Pierce Kah Hoe, additional, Wu, Suny Z., additional, Al-Eryani, Ghamdan, additional, Roden, Daniel, additional, Swarbrick, Alexander, additional, Chan, Jerry Kok Yen, additional, Albani, Salvatore, additional, Derosa, Lisa, additional, Zitvogel, Laurence, additional, Sharma, Ankur, additional, Chen, Jinmiao, additional, Silvin, Aymeric, additional, Bertoletti, Antonio, additional, Blériot, Camille, additional, Dutertre, Charles-Antoine, additional, and Ginhoux, Florent, additional

Published
2021
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11. Immunodynamics of explanted human tumors for immuno‐oncology

Author

Dubuisson, Agathe, Fahrner, Jean Eudes, Goubet, Anne Gaëlle, Terrisse, Safae A., Voisin, Nicolas, Bayard, Charles, Lofek, Sébastien, Drubay, Damien, Bredel, Delphine, Mouraud, Séverine, Susini, Sandrine, Cogdill, Alexandria P., Rebuffet, Lucas, Ballot, Elise, Jacquelot, Nicolas, Thomas de Montpreville, Vincent, Casiraghi, Odile, Radulescu, Camélia, Ferlicot, Sophie, Figueroa, David J., Yadavilli, Sapna, Waight, Jeremy D., Ballas, Marc S., Hoos, Axel X., Condamine, Thomas, Parier, Bastien, Gaudillat, Christophe, Routy, Bertrand, Ghiringhelli, François, Derosa, Lisa, Breuskin, Ingrid, Rouanne, Mathieu, André, Fabrice, Lebacle, Cédric, Baumert, Hervé, Wislez, Marie, Fadel, Élie, Cremer, Isabelle, Albiges, Laurence, Geoerger, Birgit, Scoazec, Jean Yves, Loriot, Yohann, Kroemer, Guido, Marabelle, Aurélien, Bonvalet, Mélodie, Zitvogel, Laurence, Immunologie des tumeurs et immunothérapie (UMR 1015), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), The University of Texas M.D. Anderson Cancer Center [Houston], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, The Walter and Eliza Hall Institute of Medical Research (WEHI), Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR), Centre hospitalier Saint-Joseph [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Département de médecine oncologique [Gustave Roussy], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital Foch [Suresnes], Direction de la recherche [Gustave Roussy], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Vectorologie et thérapeutiques anti-cancéreuses [Villejuif] (UMR 8203), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse (AMMICa), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Karolinska University Hospital [Stockholm], Chancellerie des Universités de Paris Agence Nationale de la Recherche, ANR Seerave Foundation Association pour la Recherche sur le Cancer, ARC ANR‐16‐RHUS‐0008 Ligue Contre le Cancer European Commission, EC Fondation pour la Recherche Médicale, FRM Institut National Du Cancer, INCa Institut Universitaire de France, IUF European Research Council, ERC Fondation Leducq RP170067 Association pour la Recherche sur le Cancer, ARC, LZ and GK were supported by the Ligue contre le Cancer (équipe labelisée), Agence Nationale de la Recherche (ANR) francogermanique ANR‐19‐CE15‐0029, ANR Projects blancs, ANR under the frame of E‐Rare‐2, the ERA‐Net for Research on Rare Diseases, Association pour la recherche sur le cancer (ARC), Bristol‐Myers Squibb Company (International Immuno‐Oncology Network), Cancéropôle Ile‐de‐France, Chancellerie des universités de Paris (Legs Poix), Fondation pour la Recherche Médicale (FRM), a donation by Elior, the European Commission (ArtForce), the European Research Council (ERC), Fondation Carrefour, Institut National du Cancer (INCa), Inserm (HTE), Institut Universitaire de France, LeDucq Foundation, the LabEx Immuno‐Oncology, the RHU Torino Lumière (ANR‐16‐RHUS‐0008), H2020 ONCOBIOME, the Seerave Foundation, the SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE), FHU CARE, Dassault, and Badinter Philantropia, and the Paris Alliance of Cancer Research Institutes (PACRI). AC is supported by the CPRIT Research Training Program (RP170067). JEF was supported by Transgene and AGG was supported by FRM. AM has been or is currently an investigator in clinical trials sponsored by BMS, MSD, GSK/Tesaro, Janssen, Roche/Genentech, Pfizer, Astra Zeneca (AZ), Amgen. AM has been or is currently a member of Clinical Trial Scientific Steering Committee for AZ and GSK. AM has been or is currently a member of the scientific advisory board of the following companies: Merck Serono, Novartis, BMS, Symphogen, Amgen, Tesaro/GSK, Pfizer, Astra Zeneca/Medimmune, Servier, Sanofi. AM has provided Scientific & Medical Consulting to the following companies: Roche, Sanofi. AM is a member of the Data Safety and Monitoring Board for the following trial NCT02423863 (TLR3 agonist, Oncovir). AM has received research funding and or drug supply for pre‐Clinical and clinical research projects from: BMS, Boehringer Ingelheim, Idera, MSD, Fondation MSD Avenir, SIRIC (INCa‐DGOS‐Inserm_12551)., ANR-16-RHUS-0008,LUMIERE,LUMIERE(2016), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC)

Subjects
Medicine (General), [SDV]Life Sciences [q-bio], Immunology, QH426-470, Medical Oncology, immune checkpoint inhibitors, R5-920, immunomonitoring, Report, precision oncology, Neoplasms, Genetics, “in sitro” assay, Tumor Microenvironment, cancer, Humans, Immunotherapy, Prospective Studies, Reports
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., To predict cancer resistance to PD‐1 blockade and design suitable combinations of immunomodulators, a 60‐h functional in sitro assay was set up in 43 tumors that allowed calculation of the “Immune Reactivity Score (IRS)” based on 17 TCR‐dependent‐ cytokines/chemokines.

Published
2020

12. Elevated Calprotectin and Abnormal Myeloid Cell Subsets Discriminate Severe from Mild COVID-19

Author

Silvin, Aymeric, primary, Chapuis, Nicolas, additional, Dunsmore, Garett, additional, Goubet, Anne-Gaëlle, additional, Dubuisson, Agathe, additional, Derosa, Lisa, additional, Almire, Carole, additional, Hénon, Clémence, additional, Kosmider, Olivier, additional, Droin, Nathalie, additional, Rameau, Philippe, additional, Catelain, Cyril, additional, Alfaro, Alexia, additional, Dussiau, Charles, additional, Friedrich, Chloé, additional, Sourdeau, Elise, additional, Marin, Nathalie, additional, Szwebel, Tali-Anne, additional, Cantin, Delphine, additional, Mouthon, Luc, additional, Borderie, Didier, additional, Deloger, Marc, additional, Bredel, Delphine, additional, Mouraud, Severine, additional, Drubay, Damien, additional, Andrieu, Muriel, additional, Lhonneur, Anne-Sophie, additional, Saada, Véronique, additional, Stoclin, Annabelle, additional, Willekens, Christophe, additional, Pommeret, Fanny, additional, Griscelli, Frank, additional, Ng, Lai Guan, additional, Zhang, Zheng, additional, Bost, Pierre, additional, Amit, Ido, additional, Barlesi, Fabrice, additional, Marabelle, Aurélien, additional, Pène, Frédéric, additional, Gachot, Bertrand, additional, André, Fabrice, additional, Zitvogel, Laurence, additional, Ginhoux, Florent, additional, Fontenay, Michaela, additional, and Solary, Eric, additional

Published
2020
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13. Immune responses during COVID-19 infection

Author

Melenotte, Cléa, primary, Silvin, Aymeric, additional, Goubet, Anne-Gaëlle, additional, Lahmar, Imran, additional, Dubuisson, Agathe, additional, Zumla, Alimuddin, additional, Raoult, Didier, additional, Merad, Mansouria, additional, Gachot, Bertrand, additional, Hénon, Clémence, additional, Solary, Eric, additional, Fontenay, Michaela, additional, André, Fabrice, additional, Maeurer, Markus, additional, Ippolito, Giuseppe, additional, Piacentini, Mauro, additional, Wang, Fu-Sheng, additional, Ginhoux, Florent, additional, Marabelle, Aurélien, additional, Kroemer, Guido, additional, Derosa, Lisa, additional, and Zitvogel, Laurence, additional

Published
2020
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14. Intestinal Akkermansia muciniphilapredicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer

Author

Derosa, Lisa, Routy, Bertrand, Thomas, Andrew Maltez, Iebba, Valerio, Zalcman, Gerard, Friard, Sylvie, Mazieres, Julien, Audigier-Valette, Clarisse, Moro-Sibilot, Denis, Goldwasser, François, Silva, Carolina Alves Costa, Terrisse, Safae, Bonvalet, Melodie, Scherpereel, Arnaud, Pegliasco, Hervé, Richard, Corentin, Ghiringhelli, François, Elkrief, Arielle, Desilets, Antoine, Blanc-Durand, Felix, Cumbo, Fabio, Blanco, Aitor, Boidot, Romain, Chevrier, Sandy, Daillère, Romain, Kroemer, Guido, Alla, Laurie, Pons, Nicolas, Le Chatelier, Emmanuelle, Galleron, Nathalie, Roume, Hugo, Dubuisson, Agathe, Bouchard, Nicole, Messaoudene, Meriem, Drubay, Damien, Deutsch, Eric, Barlesi, Fabrice, Planchard, David, Segata, Nicola, Martinez, Stéphanie, Zitvogel, Laurence, Soria, Jean-Charles, and Besse, Benjamin

Abstract

Aside from PD-L1 expression, biomarkers of response to immune checkpoint inhibitors (ICIs) in non-small-cell lung cancer (NSCLC) are needed. In a previous retrospective analysis, we documented that fecal Akkermansia muciniphila(Akk) was associated with clinical benefit of ICI in patients with NSCLC or kidney cancer. In the current study, we performed shotgun-metagenomics-based microbiome profiling in a large cohort of patients with advanced NSCLC (n= 338) treated with first- or second-line ICIs to prospectively validate the predictive value of fecal Akk. Baseline stool Akk was associated with increased objective response rates and overall survival in multivariate analyses, independent of PD-L1 expression, antibiotics, and performance status. Intestinal Akk was accompanied by a richer commensalism, including Eubacterium halliiand Bifidobacterium adolescentis, and a more inflamed tumor microenvironment in a subset of patients. However, antibiotic use (20% of cases) coincided with a relative dominance of Akk above 4.8% accompanied with the genus Clostridium, both associated with resistance to ICI. Our study shows significant differences in relative abundance of Akk that may represent potential biomarkers to refine patient stratification in future studies.

Published
2022
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16. Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer

Author

Lisa Derosa, Bertrand Routy, Andrew Maltez Thomas, Valerio Iebba, Gerard Zalcman, Sylvie Friard, Julien Mazieres, Clarisse Audigier-Valette, Denis Moro-Sibilot, François Goldwasser, Carolina Alves Costa Silva, Safae Terrisse, Melodie Bonvalet, Arnaud Scherpereel, Hervé Pegliasco, Corentin Richard, François Ghiringhelli, Arielle Elkrief, Antoine Desilets, Felix Blanc-Durand, Fabio Cumbo, Aitor Blanco, Romain Boidot, Sandy Chevrier, Romain Daillère, Guido Kroemer, Laurie Alla, Nicolas Pons, Emmanuelle Le Chatelier, Nathalie Galleron, Hugo Roume, Agathe Dubuisson, Nicole Bouchard, Meriem Messaoudene, Damien Drubay, Eric Deutsch, Fabrice Barlesi, David Planchard, Nicola Segata, Stéphanie Martinez, Laurence Zitvogel, Jean-Charles Soria, Benjamin Besse, Derosa, Lisa, Routy, Bertrand, Thomas, Andrew Maltez, Iebba, Valerio, Zalcman, Gerard, Friard, Sylvie, Mazieres, Julien, Audigier-Valette, Clarisse, Moro-Sibilot, Deni, Goldwasser, Françoi, Silva, Carolina Alves Costa, Terrisse, Safae, Bonvalet, Melodie, Scherpereel, Arnaud, Pegliasco, Hervé, Richard, Corentin, Ghiringhelli, Françoi, Elkrief, Arielle, Desilets, Antoine, Blanc-Durand, Felix, Cumbo, Fabio, Blanco, Aitor, Boidot, Romain, Chevrier, Sandy, Daillère, Romain, Kroemer, Guido, Alla, Laurie, Pons, Nicola, Le Chatelier, Emmanuelle, Galleron, Nathalie, Roume, Hugo, Dubuisson, Agathe, Bouchard, Nicole, Messaoudene, Meriem, Drubay, Damien, Deutsch, Eric, Barlesi, Fabrice, Planchard, David, Segata, Nicola, Martinez, Stéphanie, Zitvogel, Laurence, Soria, Jean-Charle, and Besse, Benjamin

Subjects
metagenomics, Lung Neoplasms, Microbiota, Programmed Cell Death 1 Receptor, biomarkers, kidney cancer, General Medicine, Akkermansia, patients stratification, NSCLC, General Biochemistry, Genetics and Molecular Biology, B7-H1 Antigen, Microbiome, immunotherapy, Akkermansia muciniphila, cancer, immune checkpoint inhibitors (ICIs), tumor microenvironment, Carcinoma, Non-Small-Cell Lung, Tumor Microenvironment, biomarker, Humans, metagenomic, Retrospective Studies
Abstract

Aside from PD-L1 expression, biomarkers of response to immune checkpoint inhibitors (ICIs) in non-small-cell lung cancer (NSCLC) are needed. In a previous retrospective analysis, we documented that fecal Akkermansia muciniphila (Akk) was associated with clinical benefit of ICI in patients with NSCLC or kidney cancer. In the current study, we performed shotgun-metagenomics-based microbiome profiling in a large cohort of patients with advanced NSCLC (n = 338) treated with first- or second-line ICIs to prospectively validate the predictive value of fecal Akk. Baseline stool Akk was associated with increased objective response rates and overall survival in multivariate analyses, independent of PD-L1 expression, antibiotics, and performance status. Intestinal Akk was accompanied by a richer commensalism, including Eubacterium hallii and Bifidobacterium adolescentis, and a more inflamed tumor microenvironment in a subset of patients. However, antibiotic use (20% of cases) coincided with a relative dominance of Akk above 4.8% accompanied with the genus Clostridium, both associated with resistance to ICI. Our study shows significant differences in relative abundance of Akk that may represent potential biomarkers to refine patient stratification in future studies.

Published
2020

17. Characterization of CD4 + and CD8 + T cells responses in the mixed lymphocyte reaction by flow cytometry and single cell RNA sequencing.

Author

Mangelinck A, Dubuisson A, Becht E, Dromaint-Catesson S, Fasquel M, Provost N, Walas D, Darville H, Galizzi JP, Lefebvre C, Blanc V, and Lombardi V

Subjects
Lymphocyte Culture Test, Mixed, Flow Cytometry, Sequence Analysis, RNA, CD8-Positive T-Lymphocytes, CD4-Positive T-Lymphocytes
Abstract

Background: The Mixed Lymphocyte Reaction (MLR) consists in the allogeneic co-culture of monocytes derived dendritic cells (MoDCs) with T cells from another donor. This in vitro assay is largely used for the assessment of immunotherapy compounds. Nevertheless, the phenotypic changes associated with lymphocyte responsiveness under MLR have never been thoroughly evaluated., Methods: Here, we used multiplex cytokine and chemokine assays, multiparametric flow cytometry and single cell RNA sequencing to deeply characterize T cells activation and function in the context of CD4 + - and CD8 + -specific MLR kinetics., Results: We showed that CD4 + and CD8 + T cells in MLR share common classical markers of response such as polyfunctionality, increased proliferation and CD25 expression but differ in their kinetics and amplitude of activation as well as their patterns of cytokines secretion and immune checkpoints expression. The analysis of immunoreactive Ki-67 + CD25 + T cells identified PBK, LRR1 and MYO1G as new potential markers of MLR response. Using cell-cell communication network inference and pathway analysis on single cell RNA sequencing data, we also highlighted key components of the immunological synapse occurring between T cells and the stimulatory MoDCs together with downstream signaling pathways involved in CD4 + and CD8 + T cells activation., Conclusion: These results provide a deep understanding of the kinetics of the MLR assay for CD4 + or CD8 + T cells and may allow to better characterize compounds impacting MLR and eventually identify new strategies for immunotherapy in cancer., Competing Interests: Authors AM, AD, EB, SD-C, MF, NP, DW, HD, J-PG, CL, VB and VL were employed by company Servier., (Copyright © 2024 Mangelinck, Dubuisson, Becht, Dromaint-Catesson, Fasquel, Provost, Walas, Darville, Galizzi, Lefebvre, Blanc and Lombardi.)

Published
2024
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