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2. Data from Cancer Induces a Stress Ileopathy Depending on β-Adrenergic Receptors and Promoting Dysbiosis that Contributes to Carcinogenesis

Author

Yonekura, Satoru, primary, Terrisse, Safae, primary, Alves Costa Silva, Carolina, primary, Lafarge, Antoine, primary, Iebba, Valerio, primary, Ferrere, Gladys, primary, Goubet, Anne-Gaëlle, primary, Fahrner, Jean-Eudes, primary, Lahmar, Imran, primary, Ueda, Kousuke, primary, Mansouri, Gibrail, primary, Pizzato, Eugénie, primary, Ly, Pierre, primary, Mazzenga, Marine, primary, Thelemaque, Cassandra, primary, Fidelle, Marine, primary, Jaulin, Fanny, primary, Cartry, Jérôme, primary, Deloger, Marc, primary, Aglave, Marine, primary, Droin, Nathalie, primary, Opolon, Paule, primary, Puget, Angélique, primary, Mann, Fanny, primary, Neunlist, Michel, primary, Bessard, Anne, primary, Aymeric, Laetitia, primary, Matysiak-Budnik, Tamara, primary, Bosq, Jacques, primary, Hofman, Paul, primary, Duong, Connie P.M., primary, Ugolini, Sophie, primary, Quiniou, Valentin, primary, Berrard, Sylvie, primary, Ryffel, Bernhard, primary, Kepp, Oliver, primary, Kroemer, Guido, primary, Routy, Bertrand, primary, Lordello, Leonardo, primary, Bani, Mohamed-Amine, primary, Segata, Nicola, primary, Yengej, Fjodor Yousef, primary, Clevers, Hans, primary, Scoazec, Jean-Yves, primary, Pasolli, Edoardo, primary, Derosa, Lisa, primary, and Zitvogel, Laurence, primary

Published
2023
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3. Supplementary Figure from Cancer Induces a Stress Ileopathy Depending on β-Adrenergic Receptors and Promoting Dysbiosis that Contributes to Carcinogenesis

Author

Yonekura, Satoru, primary, Terrisse, Safae, primary, Alves Costa Silva, Carolina, primary, Lafarge, Antoine, primary, Iebba, Valerio, primary, Ferrere, Gladys, primary, Goubet, Anne-Gaëlle, primary, Fahrner, Jean-Eudes, primary, Lahmar, Imran, primary, Ueda, Kousuke, primary, Mansouri, Gibrail, primary, Pizzato, Eugénie, primary, Ly, Pierre, primary, Mazzenga, Marine, primary, Thelemaque, Cassandra, primary, Fidelle, Marine, primary, Jaulin, Fanny, primary, Cartry, Jérôme, primary, Deloger, Marc, primary, Aglave, Marine, primary, Droin, Nathalie, primary, Opolon, Paule, primary, Puget, Angélique, primary, Mann, Fanny, primary, Neunlist, Michel, primary, Bessard, Anne, primary, Aymeric, Laetitia, primary, Matysiak-Budnik, Tamara, primary, Bosq, Jacques, primary, Hofman, Paul, primary, Duong, Connie P.M., primary, Ugolini, Sophie, primary, Quiniou, Valentin, primary, Berrard, Sylvie, primary, Ryffel, Bernhard, primary, Kepp, Oliver, primary, Kroemer, Guido, primary, Routy, Bertrand, primary, Lordello, Leonardo, primary, Bani, Mohamed-Amine, primary, Segata, Nicola, primary, Yengej, Fjodor Yousef, primary, Clevers, Hans, primary, Scoazec, Jean-Yves, primary, Pasolli, Edoardo, primary, Derosa, Lisa, primary, and Zitvogel, Laurence, primary

Published
2023
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4. Supplementary Figure 1 from Cancer-Induced Immunosuppression: IL-18–Elicited Immunoablative NK Cells

Author

Terme, Magali, primary, Ullrich, Evelyn, primary, Aymeric, Laetitia, primary, Meinhardt, Kathrin, primary, Coudert, Jérôme D., primary, Desbois, Mélanie, primary, Ghiringhelli, François, primary, Viaud, Sophie, primary, Ryffel, Bernard, primary, Yagita, Hideo, primary, Chen, Lieping, primary, Mécheri, Salaheddine, primary, Kaplanski, Gilles, primary, Prévost-Blondel, Armelle, primary, Kato, Masashi, primary, Schultze, Joachim L., primary, Tartour, Eric, primary, Kroemer, Guido, primary, Degli-Esposti, Mariapia, primary, Chaput, Nathalie, primary, and Zitvogel, Laurence, primary

Published
2023
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5. Supplementary Table 2 from Cancer-Induced Immunosuppression: IL-18–Elicited Immunoablative NK Cells

Author

Terme, Magali, primary, Ullrich, Evelyn, primary, Aymeric, Laetitia, primary, Meinhardt, Kathrin, primary, Coudert, Jérôme D., primary, Desbois, Mélanie, primary, Ghiringhelli, François, primary, Viaud, Sophie, primary, Ryffel, Bernard, primary, Yagita, Hideo, primary, Chen, Lieping, primary, Mécheri, Salaheddine, primary, Kaplanski, Gilles, primary, Prévost-Blondel, Armelle, primary, Kato, Masashi, primary, Schultze, Joachim L., primary, Tartour, Eric, primary, Kroemer, Guido, primary, Degli-Esposti, Mariapia, primary, Chaput, Nathalie, primary, and Zitvogel, Laurence, primary

Published
2023
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6. Supplementary Figure 1 from IL-18 Induces PD-1–Dependent Immunosuppression in Cancer

Author

Terme, Magali, primary, Ullrich, Evelyn, primary, Aymeric, Laetitia, primary, Meinhardt, Kathrin, primary, Desbois, Mélanie, primary, Delahaye, Nicolas, primary, Viaud, Sophie, primary, Ryffel, Bernard, primary, Yagita, Hideo, primary, Kaplanski, Gilles, primary, Prévost-Blondel, Armelle, primary, Kato, Masashi, primary, Schultze, Joachim L., primary, Tartour, Eric, primary, Kroemer, Guido, primary, Chaput, Nathalie, primary, and Zitvogel, Laurence, primary

Published
2023
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7. Supplementary Figures 1 - 7 from CCL2/CCR2-Dependent Recruitment of Functional Antigen-Presenting Cells into Tumors upon Chemotherapy

Author

Ma, Yuting, primary, Mattarollo, Stephen R., primary, Adjemian, Sandy, primary, Yang, Heng, primary, Aymeric, Laetitia, primary, Hannani, Dalil, primary, Portela Catani, João Paulo, primary, Duret, Helene, primary, Teng, Michele W.L., primary, Kepp, Oliver, primary, Wang, Yidan, primary, Sistigu, Antonella, primary, Schultze, Joachim L., primary, Stoll, Gautier, primary, Galluzzi, Lorenzo, primary, Zitvogel, Laurence, primary, Smyth, Mark J., primary, and Kroemer, Guido, primary

Published
2023
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8. Supplementary Table 1 from Cancer-Induced Immunosuppression: IL-18–Elicited Immunoablative NK Cells

Author

Terme, Magali, primary, Ullrich, Evelyn, primary, Aymeric, Laetitia, primary, Meinhardt, Kathrin, primary, Coudert, Jérôme D., primary, Desbois, Mélanie, primary, Ghiringhelli, François, primary, Viaud, Sophie, primary, Ryffel, Bernard, primary, Yagita, Hideo, primary, Chen, Lieping, primary, Mécheri, Salaheddine, primary, Kaplanski, Gilles, primary, Prévost-Blondel, Armelle, primary, Kato, Masashi, primary, Schultze, Joachim L., primary, Tartour, Eric, primary, Kroemer, Guido, primary, Degli-Esposti, Mariapia, primary, Chaput, Nathalie, primary, and Zitvogel, Laurence, primary

Published
2023
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9. Supplementary Figure 3 from Cancer-Induced Immunosuppression: IL-18–Elicited Immunoablative NK Cells

Author

Terme, Magali, primary, Ullrich, Evelyn, primary, Aymeric, Laetitia, primary, Meinhardt, Kathrin, primary, Coudert, Jérôme D., primary, Desbois, Mélanie, primary, Ghiringhelli, François, primary, Viaud, Sophie, primary, Ryffel, Bernard, primary, Yagita, Hideo, primary, Chen, Lieping, primary, Mécheri, Salaheddine, primary, Kaplanski, Gilles, primary, Prévost-Blondel, Armelle, primary, Kato, Masashi, primary, Schultze, Joachim L., primary, Tartour, Eric, primary, Kroemer, Guido, primary, Degli-Esposti, Mariapia, primary, Chaput, Nathalie, primary, and Zitvogel, Laurence, primary

Published
2023
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10. Supplementary Figure 2 from IL-18 Induces PD-1–Dependent Immunosuppression in Cancer

Author

Terme, Magali, primary, Ullrich, Evelyn, primary, Aymeric, Laetitia, primary, Meinhardt, Kathrin, primary, Desbois, Mélanie, primary, Delahaye, Nicolas, primary, Viaud, Sophie, primary, Ryffel, Bernard, primary, Yagita, Hideo, primary, Kaplanski, Gilles, primary, Prévost-Blondel, Armelle, primary, Kato, Masashi, primary, Schultze, Joachim L., primary, Tartour, Eric, primary, Kroemer, Guido, primary, Chaput, Nathalie, primary, and Zitvogel, Laurence, primary

Published
2023
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11. Data from CCL2/CCR2-Dependent Recruitment of Functional Antigen-Presenting Cells into Tumors upon Chemotherapy

Author

Ma, Yuting, primary, Mattarollo, Stephen R., primary, Adjemian, Sandy, primary, Yang, Heng, primary, Aymeric, Laetitia, primary, Hannani, Dalil, primary, Portela Catani, João Paulo, primary, Duret, Helene, primary, Teng, Michele W.L., primary, Kepp, Oliver, primary, Wang, Yidan, primary, Sistigu, Antonella, primary, Schultze, Joachim L., primary, Stoll, Gautier, primary, Galluzzi, Lorenzo, primary, Zitvogel, Laurence, primary, Smyth, Mark J., primary, and Kroemer, Guido, primary

Published
2023
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12. Supplementary Figure 2 from Cancer-Induced Immunosuppression: IL-18–Elicited Immunoablative NK Cells

Author

Terme, Magali, primary, Ullrich, Evelyn, primary, Aymeric, Laetitia, primary, Meinhardt, Kathrin, primary, Coudert, Jérôme D., primary, Desbois, Mélanie, primary, Ghiringhelli, François, primary, Viaud, Sophie, primary, Ryffel, Bernard, primary, Yagita, Hideo, primary, Chen, Lieping, primary, Mécheri, Salaheddine, primary, Kaplanski, Gilles, primary, Prévost-Blondel, Armelle, primary, Kato, Masashi, primary, Schultze, Joachim L., primary, Tartour, Eric, primary, Kroemer, Guido, primary, Degli-Esposti, Mariapia, primary, Chaput, Nathalie, primary, and Zitvogel, Laurence, primary

Published
2023
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13. Supplementary Figure Legend from CCL2/CCR2-Dependent Recruitment of Functional Antigen-Presenting Cells into Tumors upon Chemotherapy

Author

Ma, Yuting, primary, Mattarollo, Stephen R., primary, Adjemian, Sandy, primary, Yang, Heng, primary, Aymeric, Laetitia, primary, Hannani, Dalil, primary, Portela Catani, João Paulo, primary, Duret, Helene, primary, Teng, Michele W.L., primary, Kepp, Oliver, primary, Wang, Yidan, primary, Sistigu, Antonella, primary, Schultze, Joachim L., primary, Stoll, Gautier, primary, Galluzzi, Lorenzo, primary, Zitvogel, Laurence, primary, Smyth, Mark J., primary, and Kroemer, Guido, primary

Published
2023
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15. Data from IL-18 Induces PD-1–Dependent Immunosuppression in Cancer

Author

Terme, Magali, primary, Ullrich, Evelyn, primary, Aymeric, Laetitia, primary, Meinhardt, Kathrin, primary, Desbois, Mélanie, primary, Delahaye, Nicolas, primary, Viaud, Sophie, primary, Ryffel, Bernard, primary, Yagita, Hideo, primary, Kaplanski, Gilles, primary, Prévost-Blondel, Armelle, primary, Kato, Masashi, primary, Schultze, Joachim L., primary, Tartour, Eric, primary, Kroemer, Guido, primary, Chaput, Nathalie, primary, and Zitvogel, Laurence, primary

Published
2023
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16. Supplementary Figure 4 from Cancer-Induced Immunosuppression: IL-18–Elicited Immunoablative NK Cells

Author

Terme, Magali, primary, Ullrich, Evelyn, primary, Aymeric, Laetitia, primary, Meinhardt, Kathrin, primary, Coudert, Jérôme D., primary, Desbois, Mélanie, primary, Ghiringhelli, François, primary, Viaud, Sophie, primary, Ryffel, Bernard, primary, Yagita, Hideo, primary, Chen, Lieping, primary, Mécheri, Salaheddine, primary, Kaplanski, Gilles, primary, Prévost-Blondel, Armelle, primary, Kato, Masashi, primary, Schultze, Joachim L., primary, Tartour, Eric, primary, Kroemer, Guido, primary, Degli-Esposti, Mariapia, primary, Chaput, Nathalie, primary, and Zitvogel, Laurence, primary

Published
2023
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18. Data from Cancer-Induced Immunosuppression: IL-18–Elicited Immunoablative NK Cells

Author

Terme, Magali, primary, Ullrich, Evelyn, primary, Aymeric, Laetitia, primary, Meinhardt, Kathrin, primary, Coudert, Jérôme D., primary, Desbois, Mélanie, primary, Ghiringhelli, François, primary, Viaud, Sophie, primary, Ryffel, Bernard, primary, Yagita, Hideo, primary, Chen, Lieping, primary, Mécheri, Salaheddine, primary, Kaplanski, Gilles, primary, Prévost-Blondel, Armelle, primary, Kato, Masashi, primary, Schultze, Joachim L., primary, Tartour, Eric, primary, Kroemer, Guido, primary, Degli-Esposti, Mariapia, primary, Chaput, Nathalie, primary, and Zitvogel, Laurence, primary

Published
2023
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19. Supplementary Figure Legends 1-4 from Cancer-Induced Immunosuppression: IL-18–Elicited Immunoablative NK Cells

Author

Terme, Magali, primary, Ullrich, Evelyn, primary, Aymeric, Laetitia, primary, Meinhardt, Kathrin, primary, Coudert, Jérôme D., primary, Desbois, Mélanie, primary, Ghiringhelli, François, primary, Viaud, Sophie, primary, Ryffel, Bernard, primary, Yagita, Hideo, primary, Chen, Lieping, primary, Mécheri, Salaheddine, primary, Kaplanski, Gilles, primary, Prévost-Blondel, Armelle, primary, Kato, Masashi, primary, Schultze, Joachim L., primary, Tartour, Eric, primary, Kroemer, Guido, primary, Degli-Esposti, Mariapia, primary, Chaput, Nathalie, primary, and Zitvogel, Laurence, primary

Published
2023
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22. Anticancer Chemotherapy-Induced Intratumoral Recruitment and Differentiation of Antigen-Presenting Cells

Author

Ma, Yuting, Adjemian, Sandy, Mattarollo, Stephen R., Yamazaki, Takahiro, Aymeric, Laetitia, Yang, Heng, Portela Catani, João Paulo, Hannani, Dalil, Duret, Helene, Steegh, Kim, Martins, Isabelle, Schlemmer, Frederic, Michaud, Mickaël, Kepp, Oliver, Sukkurwala, Abdul Qader, Menger, Laurie, Vacchelli, Erika, Droin, Nathalie, Galluzzi, Lorenzo, Krzysiek, Roman, Gordon, Siamon, Taylor, Philip R., Van Endert, Peter, Solary, Eric, Smyth, Mark J., Zitvogel, Laurence, and Kroemer, Guido

Published
2013
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25. Cancer induces a stress ileopathy depending on B-adrenergic receptors and promoting dysbiosis that contribute to carcinogenesis

Author

Yonekura, Satoru, Terrisse, Safae, Alves Costa Silva, Carolina, Lafarge, Antoine, Iebba, Valerio, Ferrere, Gladys, Goubet, Anne-Gaelle, Fahrner, Jean-Eudes, Lahmar, Imran, Ueda, Kosuke, Mansouri, Gibrail, Pizzato, Eugenie, Ly, Pierre, Mazzenga, Marine, Thelemaque, Cassandra, Fidelle, Marine, Jaulin, Fanny, Cartry, Jerome, Deloger, Marc, Aglave, Marine, Droin, Nathalie, Opolon, Paule, Puget, Angelique, Mann, Fanny, Neunlist, Michel, Bessard, Anne, Aymeric, Laetitia, Matysiak-Budnik, Tamara, Bosq, Jacques, Hofman, Paul, Duong, Connie P M, Ugolini, Sophie, Quiniou, Valentin, Berrard, Sylvie, Ryffel, Bernhard, Kepp, Oliver, Kroemer, Guido, Routy, Bertrand, Lordello, Leonardo, Bani, Mohamed-Amine, Segata, Nicola, Yousef Yengej, Fjodor, Clevers, Hans, Scoazec, Jean-Yves, Pasolli, Edoardo, Derosa, Lisa, Zitvogel, Laurence, Yonekura, Satoru, Terrisse, Safae, Alves Costa Silva, Carolina, Lafarge, Antoine, Iebba, Valerio, Ferrere, Gladys, Goubet, Anne-Gaelle, Fahrner, Jean-Eudes, Lahmar, Imran, Ueda, Kosuke, Mansouri, Gibrail, Pizzato, Eugenie, Ly, Pierre, Mazzenga, Marine, Thelemaque, Cassandra, Fidelle, Marine, Jaulin, Fanny, Cartry, Jerome, Deloger, Marc, Aglave, Marine, Droin, Nathalie, Opolon, Paule, Puget, Angelique, Mann, Fanny, Neunlist, Michel, Bessard, Anne, Aymeric, Laetitia, Matysiak-Budnik, Tamara, Bosq, Jacques, Hofman, Paul, Duong, Connie P M, Ugolini, Sophie, Quiniou, Valentin, Berrard, Sylvie, Ryffel, Bernhard, Kepp, Oliver, Kroemer, Guido, Routy, Bertrand, Lordello, Leonardo, Bani, Mohamed-Amine, Segata, Nicola, Yousef Yengej, Fjodor, Clevers, Hans, Scoazec, Jean-Yves, Pasolli, Edoardo, Derosa, Lisa, and Zitvogel, Laurence

Abstract

Gut dysbiosis has been associated with intestinal and extra-intestinal malignancies but whether and how carcinogenesis drives compositional shifts of the microbiome to its own benefit remains an open conundrum. Here we show that malignant processes can cause ileal mucosa atrophy, with villous microvascular constriction associated with dominance of sympathetic over cholinergic signaling. Rapid onset of tumorigenesis induced a burst of Reg3y release by ileal cells, and transient epithelial barrier permeability that culminated in overt and long lasting dysbiosis dominated by Gram positive Clostridium species. Pharmacological blockade of B-adrenergic receptors or genetic deficiency in Adrb2 gene, vancomycin or co-housing of tumor bearers with tumor free littermates prevented cancer-induced ileopathy, eventually slowing tumor growth kinetics. Cancer patients harbor distinct hallmarks of this stress ileopathy dominated by Clostridium species. Hence, stress ileopathy is a corollary disease of extra-intestinal malignancies requiring specific therapies.

Published
2022

26. Cancer Induces a Stress Ileopathy Depending on beta-Adrenergic Receptors and Promoting Dysbiosis that Contributes to Carcinogenesis

Author

Nefro Vasculaire Geneeskunde, CMM, Cancer, Hubrecht Institute with UMC, Yonekura, Satoru, Terrisse, Safae, Silva, Carolina Alves Costa, Lafarge, Antoine, Iebba, Valerio, Ferrere, Gladys, Goubet, Anne Gaëlle, Fahrner, Jean Eudes, Lahmar, Imran, Ueda, Kousuke, Mansouri, Gibrail, Pizzato, Eugénie, Ly, Pierre, Mazzenga, Marine, Thelemaque, Cassandra, Fidelle, Marine, Jaulin, Fanny, Cartry, Jérôme, Deloger, Marc, Aglave, Marine, Droin, Nathalie, Opolon, Paule, Puget, Angélique, Mann, Fanny, Neunlist, Michel, Bessard, Anne, Aymeric, Laetitia, Matysiak-Budnik, Tamara, Bosq, Jacques, Hofman, Paul, Duong, Connie P.M., Ugolini, Sophie, Quiniou, Valentin, Berrard, Sylvie, Ryffel, Bernhard, Kepp, Oliver, Kroemer, Guido, Routy, Bertrand, Lordello, Leonardo, Bani, Mohamed Amine, Segata, Nicola, Yengej, Fjodor Yousef, Clevers, Hans, Scoazec, Jean Yves, Pasolli, Edoardo, Derosa, Lisa, Zitvogel, Laurence, Nefro Vasculaire Geneeskunde, CMM, Cancer, Hubrecht Institute with UMC, Yonekura, Satoru, Terrisse, Safae, Silva, Carolina Alves Costa, Lafarge, Antoine, Iebba, Valerio, Ferrere, Gladys, Goubet, Anne Gaëlle, Fahrner, Jean Eudes, Lahmar, Imran, Ueda, Kousuke, Mansouri, Gibrail, Pizzato, Eugénie, Ly, Pierre, Mazzenga, Marine, Thelemaque, Cassandra, Fidelle, Marine, Jaulin, Fanny, Cartry, Jérôme, Deloger, Marc, Aglave, Marine, Droin, Nathalie, Opolon, Paule, Puget, Angélique, Mann, Fanny, Neunlist, Michel, Bessard, Anne, Aymeric, Laetitia, Matysiak-Budnik, Tamara, Bosq, Jacques, Hofman, Paul, Duong, Connie P.M., Ugolini, Sophie, Quiniou, Valentin, Berrard, Sylvie, Ryffel, Bernhard, Kepp, Oliver, Kroemer, Guido, Routy, Bertrand, Lordello, Leonardo, Bani, Mohamed Amine, Segata, Nicola, Yengej, Fjodor Yousef, Clevers, Hans, Scoazec, Jean Yves, Pasolli, Edoardo, Derosa, Lisa, and Zitvogel, Laurence

Published
2022

29. Cancer cell–autonomous contribution of type I interferon signaling to the efficacy of chemotherapy

Author

Sistigu, Antonella, Yamazaki, Takahiro, Vacchelli, Erika, Chaba, Kariman, Enot, David P, Adam, Julien, Vitale, Ilio, Goubar, Aicha, Baracco, Elisa E, Remédios, Catarina, Fend, Laetitia, Hannani, Dalil, Aymeric, Laetitia, Ma, Yuting, Niso-Santano, Mireia, Kepp, Oliver, Schultze, Joachim L, Tüting, Thomas, Belardelli, Filippo, Bracci, Laura, La Sorsa, Valentina, Ziccheddu, Giovanna, Sestili, Paola, Urbani, Francesca, Delorenzi, Mauro, Lacroix-Triki, Magali, Quidville, Virginie, Conforti, Rosa, Spano, Jean-Philippe, Pusztai, Lajos, Poirier-Colame, Vichnou, Delaloge, Suzette, Penault-Llorca, Frederique, Ladoire, Sylvain, Arnould, Laurent, Cyrta, Joanna, Dessoliers, Marie-Charlotte, Eggermont, Alexander, Bianchi, Marco E, Pittet, Mikael, Engblom, Camilla, Pfirschke, Christina, Préville, Xavier, Uzè, Gilles, Schreiber, Robert D, Chow, Melvyn T, Smyth, Mark J, Proietti, Enrico, André, Fabrice, Kroemer, Guido, and Zitvogel, Laurence

Published
2014
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31. Fecal Supernatant from Adult with Autism Spectrum Disorder Alters Digestive Functions, Intestinal Epithelial Barrier, and Enteric Nervous System

Author

Gonzales, Jacques, Marchix, Justine, Aymeric, Laetitia, Le Berre-Scoul, Catherine, Zoppi, Johanna, Bordron, Philippe, Burel, Marie, Davidovic, Laetitia, Richard, Jean-Romain, Gaman, Alexandru, Lejuste, Florian, Brouillet, Julie, Le Vacon, Françoise, Chaffron, Samuel, Leboyer, Marion, Boudin, Hélène, Neunlist, Michel, The Enteric Nervous System in gut and brain disorders [U1235] (TENS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Fondation FondaMental [Créteil], Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Henri Mondor, Biofortis Mérieux NutriSciences [Saint-Herblain], Laboratoire des Sciences du Numérique de Nantes (LS2N), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), and NantesU M, Dépôt

Subjects
[SDV] Life Sciences [q-bio], enteric nervous system, QH301-705.5, intestinal permeability, [SDV]Life Sciences [q-bio], mental disorders, microbiota, autism, Biology (General), Article, bacterial metabolite
Abstract

International audience; Autism Spectrum Disorders (ASDs) are neurodevelopmental disorders defined by impaired social interactions and communication with repetitive behaviors, activities, or interests. Gastrointestinal (GI) disturbances and gut microbiota dysbiosis are frequently associated with ASD in childhood. However, it is not known whether microbiota dysbiosis in ASD patients also occurs in adulthood. Further, the consequences of altered gut microbiota on digestive functions and the enteric nervous system (ENS) remain unexplored. Therefore, we studied, in mice, the ability offecal supernatant (FS) from adult ASD patients to induce GI dysfunctions and ENS remodeling. First, the analyses of the fecal microbiota composition in adult ASD patients indicated a reduced α-diversity and increased abundance of three bacterial 16S rRNA gene amplicon sequence variants compared to healthy controls (HC). The transfer of FS from ASD patients (FS–ASD) to mice decreased colonic barrier permeability by 29% and 58% compared to FS–HC for paracellular and transcellular permeability, respectively. These effects are associated with the reduced expression of the tight junction proteins JAM-A, ZO-2, cingulin, and proinflammatory cytokines TNFα and IL1β. In addition, the expression of glial and neuronal molecules was reduced by FS–ASD as compared to FS-HC in particular for those involved in neuronal connectivity (βIII-tubulin and synapsin decreased by 31% and 67%, respectively). Our data suggest that changes in microbiota composition in ASD may contribute to GI alterations, and in part, via ENS remodeling.

Published
2021
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32. Cancer Induces a Stress Ileopathy Depending on β-Adrenergic Receptors and Promoting Dysbiosis that Contributes to Carcinogenesis

Author

Yonekura, Satoru, primary, Terrisse, Safae, additional, Alves Costa Silva, Carolina, additional, Lafarge, Antoine, additional, Iebba, Valerio, additional, Ferrere, Gladys, additional, Goubet, Anne-Gaëlle, additional, Fahrner, Jean-Eudes, additional, Lahmar, Imran, additional, Ueda, Kousuke, additional, Mansouri, Gibrail, additional, Pizzato, Eugénie, additional, Ly, Pierre, additional, Mazzenga, Marine, additional, Thelemaque, Cassandra, additional, Fidelle, Marine, additional, Jaulin, Fanny, additional, Cartry, Jérôme, additional, Deloger, Marc, additional, Aglave, Marine, additional, Droin, Nathalie, additional, Opolon, Paule, additional, Puget, Angélique, additional, Mann, Fanny, additional, Neunlist, Michel, additional, Bessard, Anne, additional, Aymeric, Laetitia, additional, Matysiak-Budnik, Tamara, additional, Bosq, Jacques, additional, Hofman, Paul, additional, Duong, Connie P.M., additional, Ugolini, Sophie, additional, Quiniou, Valentin, additional, Berrard, Sylvie, additional, Ryffel, Bernhard, additional, Kepp, Oliver, additional, Kroemer, Guido, additional, Routy, Bertrand, additional, Lordello, Leonardo, additional, Bani, Mohamed-Amine, additional, Segata, Nicola, additional, Yengej, Fjodor Yousef, additional, Clevers, Hans, additional, Scoazec, Jean-Yves, additional, Pasolli, Edoardo, additional, Derosa, Lisa, additional, and Zitvogel, Laurence, additional

Published
2021
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33. Contributors

Author

Abadie, Valérie, primary, Abraham, Clara, additional, Adams, David H., additional, Agace, William W., additional, Alexander-Brett, Jennifer, additional, Alkhairy, Omar, additional, Ambite, Ines, additional, Anderson, Deborah J., additional, Artis, David, additional, Atmar, Robert L., additional, Aymeric, Laetitia, additional, Bachert, Claus, additional, Bakema, Jantine E., additional, Baker, Kristi, additional, Beagley, Kenneth W., additional, Befus, A.D., additional, Bemark, Mats, additional, Berin, M. Cecilia, additional, Berings, Margot, additional, Berzofsky, Jay A., additional, Bilej, Martin, additional, Biswas, Nabanita, additional, Blumberg, Richard S., additional, Bienenstock, John, additional, Bogdanos, Dimitrios, additional, Boirivant, Monica, additional, Boonnak, Kobporn, additional, Bracke, Ken R., additional, Brandtzaeg, Per, additional, Braun, Jonathan, additional, Bringer, Marie-Agnès, additional, Broadbent, Andrew J., additional, Bronson, Richard, additional, Brusselle, Guy G., additional, Bulmer, Judith N., additional, Butler, J.E., additional, Cardenas, Paul A., additional, Cebra, John J., additional, Cella, Marina, additional, Cerutti, Andrea, additional, Challacombe, Stephen J., additional, Chattha, Kuldeep, additional, Cheroutre, Hilde, additional, Chiba, Tsutomu, additional, Chorny, Alejo, additional, Clements, John D., additional, Colonna, Marco, additional, Cookson, William O.C., additional, Corbeil, Lynette B., additional, Corthésy, Blaise, additional, Cripps, Allan W., additional, van Crombruggen, Koen, additional, Pires da Cunha, Andre, additional, Cunningham-Rundles, Susanna, additional, Curtiss, Roy, additional, Darfeuille-Michaud, Arlette, additional, de Jonge, Wouter J., additional, Deban, Livija, additional, Denning, Timothy L., additional, Di Santo, James P., additional, Diefenbach, Andreas, additional, DiRita, Victor J., additional, Downey, Jordan, additional, Du, Ming-Qing, additional, Edelblum, Karen L., additional, van Egmond, Marjolein, additional, Epple, H.-J., additional, Fagarasan, Sidonia, additional, Fahey, John V., additional, Ferris, Michael J., additional, Fichtner-Feigl, Stefan, additional, Fidel, Paul L., additional, Flach, Melanie, additional, Flavell, Richard, additional, Fleit, Howard B., additional, Franchini, Genoveffa, additional, Freytag, Lucy C., additional, Fuchs, Anja, additional, Fujihashi, kohtaro, additional, Fuss, Ivan J., additional, Gagliani, Nicola, additional, Garcia, Marta Rodriguez, additional, Garrett, Wendy S., additional, Gershwin, M. Eric, additional, Gevaert, Philippe, additional, Gleeson, Maree, additional, Godaly, Gabriela, additional, Goldblum, Randall M., additional, Gour, Naina, additional, Gursel, Mayda, additional, Hajishengallis, George, additional, Hammad, Hamida, additional, Hammarström, Lennart, additional, Hänninen, Arno, additional, Hanson, Lars Å., additional, Hayday, Adrian, additional, Herzog, Ronit, additional, Hodgins, Douglas C., additional, Holgate, Stephen T., additional, Holmgren, Jan, additional, Holtzman, Michael J., additional, Hook, Edward W., additional, Huber, Samuel, additional, Hurwitz, Julia L., additional, Ivanyi, Juraj, additional, Iwasaki, Akiko, additional, Jabri, Bana, additional, Jackson, Susan, additional, Jacobs, Jonathan, additional, Jalkanen, Sirpa, additional, Janoff, Edward N., additional, Jerse, Ann E., additional, Jeyanathan, Mangalakumari, additional, Julian, Bruce A., additional, Kacskovics, Imre, additional, Kaetzel, Charlotte S., additional, Kaushic, Charu, additional, Kelsall, Brian L., additional, Kessans, Sarah, additional, Kesselring, Rebecca, additional, Kilian, Mogens, additional, Kiyono, Hiroshi, additional, Klinman, Dennis M., additional, Korotkova, Marina, additional, Kronenberg, Mitchell, additional, Krysko, Olga, additional, Kurono, Yuichi, additional, Kverka, Miloslav, additional, Lambrecht, Bart N., additional, Lamm, Michael E., additional, Lantz, Olivier, additional, Lash, Gendie E., additional, Lavelle, E.C., additional, Lefrancois, Leo, additional, Leung, Patrick S.C., additional, Levine, Myron M., additional, Lim, David J., additional, Lippolis, John, additional, Louis, Nancy A., additional, Luster, Andrew D., additional, Lutay, Nataliya, additional, Lycke, Nils, additional, Macpherson, Andrew J., additional, Mantis, Nicholas J., additional, Marcotte, Harold, additional, Martin, David H., additional, Mason, Hugh S., additional, Massa, Helen M., additional, Matoba, Nobuyuki, additional, Mayer, Lloyd, additional, Maynard, Craig L., additional, McElrath, M. Juliana, additional, McEntee, C., additional, McGhee, Jerry R., additional, McGuckin, Michael A., additional, Mestecky, Jiri, additional, Mikhak, Zamaneh, additional, Miller, Robert D., additional, Moldoveanu, Zina, additional, Montgomery, Paul C., additional, Mor, Tsafrir, additional, Neurath, Markus F., additional, Neyt, Katrijn, additional, Nicholson, Lindsay K., additional, Novak, Jan, additional, Nowicki, Stella, additional, O’Hagan, D.T., additional, O’Sullivan, Nancy L., additional, Ogra, Pearay, additional, Orihuela, Carlos, additional, Ouellette, André J., additional, Owen, Robert L., additional, Pabst, Oliver, additional, Parkos, Charles A., additional, Parreño, Viviana, additional, Patel, Mickey V., additional, Perez-Novo, Claudina, additional, Perkins, Darren J., additional, Prussin, Calman, additional, Pudney, Jeffrey, additional, Raghavan, Sukanya, additional, Rainard, Pascal, additional, Ramani, Sasirekha, additional, Randall, Troy D., additional, Raska, Milan, additional, Renukaradhya, Gourapura J., additional, Rescigno, Maria, additional, Rosenthal, Kenneth L., additional, Rothenberg, Marc E., additional, Ruemmele, Frank M., additional, Russell, Michael W., additional, Saif, Linda J., additional, Salinas, Irene, additional, Salmi, Marko, additional, Salmon, Henri, additional, Sampson, Hugh A., additional, Sansonetti, Philippe, additional, Schneider, T., additional, Serafini, Nicolas, additional, Sharma, Dolly, additional, Shen, Zheng, additional, Shi, Hai Ning, additional, Shirlaw, Penelope J., additional, Shivhare, Sourima B., additional, Smith, Phillip D., additional, Smith, Patrick M., additional, Smith, Daniel J., additional, Smythies, Lesley E., additional, Spencer, Jo, additional, Strober, Warren, additional, Subbarao, Kanta, additional, Svanborg, Catharina, additional, Svennerholm, Ann-Mari, additional, Taubman, Martin A., additional, Telemo, Esbjörn, additional, Thornhill, Martin H., additional, Thornton, David J., additional, Thuenemann, Eva, additional, Tlaskalova-Hogenova, Helena, additional, Tristram, Debra, additional, Trivedi, Palak, additional, Tuomanen, Elaine, additional, Turanek, Jaroslav, additional, Turner, Jerrold R., additional, Underdown, Brian J., additional, van Helden, Mary J., additional, Veazey, Ronald S., additional, Verdu, Elena F., additional, Vlasova, Anastasia, additional, Vliagoftis, Harissios, additional, Vogel, Stefanie N., additional, Walker, W. Allan, additional, Wang, Xiaolei, additional, Watanabe, Tomohiro, additional, Weaver, Casey T., additional, Weiner, Howard L., additional, Wells, Jerry M., additional, Wen, Ting, additional, Whittum-Hudson, Judith, additional, Whitsett, Jeffrey A., additional, Williams, Ifor R., additional, Wills-Karp, Marsha, additional, Wira, Charles R., additional, Woof, Jenny M., additional, Wotherspoon, Andrew C., additional, Xing, Zhou, additional, Xu, Huanbin, additional, Zaph, Colby, additional, Zeissig, Sebastian, additional, and Zeitz, M., additional

Published
2015
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37. Cancer induces a stress ileopathy depending on B-adrenergic receptors and promoting dysbiosis that contribute to carcinogenesis

Author

Yonekura, Satoru, Terrisse, Safae, Alves Costa Silva, Carolina, Lafarge, Antoine, Iebba, Valerio, Ferrere, Gladys, Goubet, Anne-Gaelle, Fahrner, Jean-Eudes, Lahmar, Imran, Ueda, Kosuke, Mansouri, Gibrail, Pizzato, Eugenie, Ly, Pierre, Mazzenga, Marine, Thelemaque, Cassandra, Fidelle, Marine, Jaulin, Fanny, Cartry, Jerome, Deloger, Marc, Aglave, Marine, Droin, Nathalie, Opolon, Paule, Puget, Angelique, Mann, Fanny, Neunlist, Michel, Bessard, Anne, Aymeric, Laetitia, Matysiak-Budnik, Tamara, Bosq, Jacques, Hofman, Paul, Duong, Connie P M, Ugolini, Sophie, Quiniou, Valentin, Berrard, Sylvie, Ryffel, Bernhard, Kepp, Oliver, Kroemer, Guido, Routy, Bertrand, Lordello, Leonardo, Bani, Mohamed-Amine, Segata, Nicola, Yousef Yengej, Fjodor, Clevers, Hans, Scoazec, Jean-Yves, Pasolli, Edoardo, Derosa, Lisa, Zitvogel, Laurence, Yonekura, Satoru, Terrisse, Safae, Alves Costa Silva, Carolina, Lafarge, Antoine, Iebba, Valerio, Ferrere, Gladys, Goubet, Anne-Gaelle, Fahrner, Jean-Eudes, Lahmar, Imran, Ueda, Kosuke, Mansouri, Gibrail, Pizzato, Eugenie, Ly, Pierre, Mazzenga, Marine, Thelemaque, Cassandra, Fidelle, Marine, Jaulin, Fanny, Cartry, Jerome, Deloger, Marc, Aglave, Marine, Droin, Nathalie, Opolon, Paule, Puget, Angelique, Mann, Fanny, Neunlist, Michel, Bessard, Anne, Aymeric, Laetitia, Matysiak-Budnik, Tamara, Bosq, Jacques, Hofman, Paul, Duong, Connie P M, Ugolini, Sophie, Quiniou, Valentin, Berrard, Sylvie, Ryffel, Bernhard, Kepp, Oliver, Kroemer, Guido, Routy, Bertrand, Lordello, Leonardo, Bani, Mohamed-Amine, Segata, Nicola, Yousef Yengej, Fjodor, Clevers, Hans, Scoazec, Jean-Yves, Pasolli, Edoardo, Derosa, Lisa, and Zitvogel, Laurence

Abstract

Gut dysbiosis has been associated with intestinal and extra-intestinal malignancies but whether and how carcinogenesis drives compositional shifts of the microbiome to its own benefit remains an open conundrum. Here we show that malignant processes can cause ileal mucosa atrophy, with villous microvascular constriction associated with dominance of sympathetic over cholinergic signaling. Rapid onset of tumorigenesis induced a burst of Reg3y release by ileal cells, and transient epithelial barrier permeability that culminated in overt and long lasting dysbiosis dominated by Gram positive Clostridium species. Pharmacological blockade of B-adrenergic receptors or genetic deficiency in Adrb2 gene, vancomycin or co-housing of tumor bearers with tumor free littermates prevented cancer-induced ileopathy, eventually slowing tumor growth kinetics. Cancer patients harbor distinct hallmarks of this stress ileopathy dominated by Clostridium species. Hence, stress ileopathy is a corollary disease of extra-intestinal malignancies requiring specific therapies.

Published
2021

38. Desirable cell death during anticancer chemotherapy

Author

Locher, Clara, Conforti, Rosa, Aymeric, Laetitia, Ma, Yuting, Yamazaki, Takahiro, Rusakiewicz, Sylvie, Tesnière, Antoine, Ghiringhelli, François, Apetoh, Lionel, Morel, Yannis, Girard, Jean-Philippe, Kroemer, Guido, and Zitvogel, Laurence

Published
2010
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42. Colorectal cancer specific conditions promote Streptococcus gallolyticus gut colonization

Author

Aymeric, Laetitia, primary, Donnadieu, Françoise, additional, Mulet, Céline, additional, du Merle, Laurence, additional, Nigro, Giulia, additional, Saffarian, Azadeh, additional, Bérard, Marion, additional, Poyart, Claire, additional, Robine, Sylvie, additional, Regnault, Béatrice, additional, Trieu-Cuot, Patrick, additional, Sansonetti, Philippe J., additional, and Dramsi, Shaynoor, additional

Published
2017
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43. The immunogenicity of cell death induced by anti-cancer chemotherapy

Author

Aymeric, Laetitia, 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), Université Paris Sud - Paris XI, Laurence Zitvogel, STAR, ABES, and Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
[SDV.IMM] Life Sciences [q-bio]/Immunology, Inflammasome, ATP, Oxaliplatin, IL-17, NLRP3, Mort cellulaire immunogène, IL-1β, Lymphocytes T Gamma delta, Anthracyclins, [SDV.IMM]Life Sciences [q-bio]/Immunology, Anthracyclines, Oxaliplatine, Gamma delta T lymphocytes, Immunogenic cell death
Abstract

In most cases, cancer occurs in immunocompetent individuals, revealing the potential failure of the immune system to impair tumor development. Trying to restore or to induce an efficient anti-tumoral immune response is part of the main challenges of cancer treatment. In addition to the classical immunotherapeutic compounds, conventionnal cytotoxic treatments can also have some immunostimulatory effects. Among these treatments, the chemotherapeutic agents oxaliplatin and anthracyclins, as well as irradiation, can induce an immunogenic cell death, contributing to the activation of IFNγ-producing CD8 T cells. We show that upon treatment with immunogenic drugs, tumor cells are able to release ATP in the extracellular medium. This ATP can act on dendritic cells through its receptor P2RX7, which is able to activate the inflammasome NLRP3 and the subsequent production of IL-1β. Using models of transplantable tumors in mice we could show that the production of IL-1β induced by immunogenic treatments was mandatory for their efficacy. In addition to being directly involved in Tc1 cells polarization, IL-1β could promote the production of IL-17A by gamma delta T cells which were accumulating in the tumor bed following chemotherapy. We could show that these IL-17 producing gamma delta T cells were involved in treatment efficacy. This work has revealed that extracellular ATP was a crucial endogenous danger signal involved in anti-cancer chemotherapy efficacy. Furthermore, we have shown that conventionnal cytotoxic compounds could transform the smoldering pro-tumoral inflammation into an acute and immunogenic anti-tumoral one. This work may have some clinical implications, especially in the setting of therapeutic protocols involving the combination of conventionnal cytotoxic therapies with selected immunoadjuvants for the treatment of cancer., Le développement d’un cancer chez un individu immunocompétent témoigne del’inefficacité de ses défenses immunitaires naturelles à entraver la progression tumorale. Larestauration ou l’induction de réponses immunitaires anti-tumorales efficaces sont des enjeuxmajeurs des stratégies thérapeutiques actuelles. En plus des immunothérapies classiques,visant à activer le système immunitaire des patients contre leurs tumeurs, les thérapiesconventionnelles, telles que les chimiothérapies et la radiothérapie, peuvent avoir des effetsimmunostimulants, en parallèle de leur effet directement cytotoxique sur les cellulestumorales. Parmi celles-ci, les anthracyclines, l’oxaliplatine et la radiothérapie sontnotamment capables d’induire une mort cellulaire immunogène. L’efficacité thérapeutique deces traitements dépend de l’activation de lymphocytes T (LT) CD8 anti-tumoraux,producteurs d’interféron-gamma (IFN-γ). En utilisant des modèles murins de tumeurstransplantées, nous montrons que le traitement des cellules tumorales par des droguesimmunogènes induit la libération d’adénosine triphosphate (ATP) dans le milieu extracellulaire.Ce signal de danger endogène se lie à son récepteur P2RX7 sur les cellulesdendritiques et permet la formation de l’inflammasome NLRP3/ASC/pro-caspase 1,conduisant à l’activation protéolytique de la caspase 1, qui active la pro-interleukine-1β (pro-IL-1β) en interleukine-1β (IL-1β). L’IL-1β peut directement agir sur les LT CD8 pourfaciliter leur polarisation vers un phénotype de lymphocytes T cytotoxiques de type 1 (Tc1).De plus, le traitement de tumeurs établies par des drogues immunogènes induit uneproduction d’IL-17A (IL-17) dans le lit tumoral, au cours de la première semaine suivant letraitement. Les LT gamma delta (LTγδ) sont les principaux producteurs de cette cytokinedans nos modèles. Ces cellules s’accumulent transitoirement dans la tumeur dès le troisièmejour suivant le traitement et leur taux est parfaitement corrélé à celui des LT CD8 producteursd’IFN-γ tumoraux. Comme l’IFN-γ, l’IL-17 et les LTγδ sont nécessaires à l’efficacitéthérapeutique des drogues immunogènes. L’IL-1β produite par les cellules dendritiquesexposées à des corps apoptotiques immunogènes stimule directement la production d’IL-17par les LTγδ. Ces travaux ont contribué à identifier l’ATP extra-cellulaire comme undéterminant moléculaire de l’immunogénicité des cellules tumorales exposées à certainesthérapies anti-cancéreuses conventionnelles. De plus, nous montrons que les traitementscytotoxiques classiques peuvent moduler l’environnement immunitaire dans le lit tumoral, etcontribuer à remplacer une inflammation chronique et immunosuppressive en uneinflammation aigüe et immunogène. L’étude des interactions entre le système immunitaire etles thérapies anti-cancéreuses conventionnelles est nécessaire pour utiliser ces traitements demanière plus rationnelle, en les combinant par exemple à des immunothérapies plusclassiques.

Published
2011

44. Immunogénicite de la mort cellulaire induite par les chimiothérapies anti-cancéreuses

Author

Aymeric, Laetitia, Immunologie des tumeurs et immunothérapie (UMR 1015), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Sud - Paris XI, and Laurence Zitvogel

Subjects
Inflammasome, ATP, Oxaliplatin, IL-17, NLRP3, Mort cellulaire immunogène, IL-1β, Lymphocytes T Gamma delta, Anthracyclins, [SDV.IMM]Life Sciences [q-bio]/Immunology, Anthracyclines, Oxaliplatine, Gamma delta T lymphocytes, Immunogenic cell death
Abstract

In most cases, cancer occurs in immunocompetent individuals, revealing the potential failure of the immune system to impair tumor development. Trying to restore or to induce an efficient anti-tumoral immune response is part of the main challenges of cancer treatment. In addition to the classical immunotherapeutic compounds, conventionnal cytotoxic treatments can also have some immunostimulatory effects. Among these treatments, the chemotherapeutic agents oxaliplatin and anthracyclins, as well as irradiation, can induce an immunogenic cell death, contributing to the activation of IFNγ-producing CD8 T cells. We show that upon treatment with immunogenic drugs, tumor cells are able to release ATP in the extracellular medium. This ATP can act on dendritic cells through its receptor P2RX7, which is able to activate the inflammasome NLRP3 and the subsequent production of IL-1β. Using models of transplantable tumors in mice we could show that the production of IL-1β induced by immunogenic treatments was mandatory for their efficacy. In addition to being directly involved in Tc1 cells polarization, IL-1β could promote the production of IL-17A by gamma delta T cells which were accumulating in the tumor bed following chemotherapy. We could show that these IL-17 producing gamma delta T cells were involved in treatment efficacy. This work has revealed that extracellular ATP was a crucial endogenous danger signal involved in anti-cancer chemotherapy efficacy. Furthermore, we have shown that conventionnal cytotoxic compounds could transform the smoldering pro-tumoral inflammation into an acute and immunogenic anti-tumoral one. This work may have some clinical implications, especially in the setting of therapeutic protocols involving the combination of conventionnal cytotoxic therapies with selected immunoadjuvants for the treatment of cancer.; Le développement d’un cancer chez un individu immunocompétent témoigne del’inefficacité de ses défenses immunitaires naturelles à entraver la progression tumorale. Larestauration ou l’induction de réponses immunitaires anti-tumorales efficaces sont des enjeuxmajeurs des stratégies thérapeutiques actuelles. En plus des immunothérapies classiques,visant à activer le système immunitaire des patients contre leurs tumeurs, les thérapiesconventionnelles, telles que les chimiothérapies et la radiothérapie, peuvent avoir des effetsimmunostimulants, en parallèle de leur effet directement cytotoxique sur les cellulestumorales. Parmi celles-ci, les anthracyclines, l’oxaliplatine et la radiothérapie sontnotamment capables d’induire une mort cellulaire immunogène. L’efficacité thérapeutique deces traitements dépend de l’activation de lymphocytes T (LT) CD8 anti-tumoraux,producteurs d’interféron-gamma (IFN-γ). En utilisant des modèles murins de tumeurstransplantées, nous montrons que le traitement des cellules tumorales par des droguesimmunogènes induit la libération d’adénosine triphosphate (ATP) dans le milieu extracellulaire.Ce signal de danger endogène se lie à son récepteur P2RX7 sur les cellulesdendritiques et permet la formation de l’inflammasome NLRP3/ASC/pro-caspase 1,conduisant à l’activation protéolytique de la caspase 1, qui active la pro-interleukine-1β (pro-IL-1β) en interleukine-1β (IL-1β). L’IL-1β peut directement agir sur les LT CD8 pourfaciliter leur polarisation vers un phénotype de lymphocytes T cytotoxiques de type 1 (Tc1).De plus, le traitement de tumeurs établies par des drogues immunogènes induit uneproduction d’IL-17A (IL-17) dans le lit tumoral, au cours de la première semaine suivant letraitement. Les LT gamma delta (LTγδ) sont les principaux producteurs de cette cytokinedans nos modèles. Ces cellules s’accumulent transitoirement dans la tumeur dès le troisièmejour suivant le traitement et leur taux est parfaitement corrélé à celui des LT CD8 producteursd’IFN-γ tumoraux. Comme l’IFN-γ, l’IL-17 et les LTγδ sont nécessaires à l’efficacitéthérapeutique des drogues immunogènes. L’IL-1β produite par les cellules dendritiquesexposées à des corps apoptotiques immunogènes stimule directement la production d’IL-17par les LTγδ. Ces travaux ont contribué à identifier l’ATP extra-cellulaire comme undéterminant moléculaire de l’immunogénicité des cellules tumorales exposées à certainesthérapies anti-cancéreuses conventionnelles. De plus, nous montrons que les traitementscytotoxiques classiques peuvent moduler l’environnement immunitaire dans le lit tumoral, etcontribuer à remplacer une inflammation chronique et immunosuppressive en uneinflammation aigüe et immunogène. L’étude des interactions entre le système immunitaire etles thérapies anti-cancéreuses conventionnelles est nécessaire pour utiliser ces traitements demanière plus rationnelle, en les combinant par exemple à des immunothérapies plusclassiques.

Published
2011

47. Liste des auteurs

Author

Lecerf, Jean-Michel, Delzenne, Nathalie, Aires, Julio, Aron-Wisnewsky, Judith, Aymeric, Laetitia, Benitez, Antonio, Bernalier-Donadille, Annick, Berthelot, Laureline, Bertrand, Léo, Bindels, Laure B., Bodinier, Marie, Boudin, Hélène, Brosseau, Carole, Burcelin, Rémy, Butel, Marie-José, Chassaing, Benoît, Clément, Karine, Daniel, Noëmie, Déchelotte, Pierre, Degraeve, Alexandra L., Desreumaux, Pierre, Doré, Joël, Eutamene, Héléne, Everard, Amandine, Foligné, Benoit, Gérard, Philippe, Godet, Murielle, Grangette, Corinne, Janoir, Claire, Jubelin, Grégory, Kordahi, Melissa, Kropp, Camille, Langella, Philippe, Layé, Sophie, Le Roy, Tiphaine, Leclercq, Sophie, Lehuen, Agnès, Lepage, Patricia, Leulier, François, Marchix, Justine, Marteau, Philippe, Martin, Rebeca, Mithieux, Gilles, De Gouveia, Maria-Ines Moreira, Naimi, Sabrine, Neunlist, Michel, Neyrinck, Audrey, Olier, Maïwenn, Ribet, David, Rimbaud, Pierre, Roberfroid, Marcel, Rouland, Matthieu, Sobhani, Iradj, Theodorou, Vassilia, Thierry, Anne, Titécat, Marie, Trottein, François, Valence, Florence, and Vidal, Hubert

Published
2021
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48. CCL2/CCR2-Dependent Recruitment of Functional Antigen-Presenting Cells into Tumors upon Chemotherapy

Author

Ma, Yuting, primary, Mattarollo, Stephen R., additional, Adjemian, Sandy, additional, Yang, Heng, additional, Aymeric, Laetitia, additional, Hannani, Dalil, additional, Portela Catani, João Paulo, additional, Duret, Helene, additional, Teng, Michele W.L., additional, Kepp, Oliver, additional, Wang, Yidan, additional, Sistigu, Antonella, additional, Schultze, Joachim L., additional, Stoll, Gautier, additional, Galluzzi, Lorenzo, additional, Zitvogel, Laurence, additional, Smyth, Mark J., additional, and Kroemer, Guido, additional

Published
2014
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49. Cancer-Induced Immunosuppression: IL-18–Elicited Immunoablative NK Cells

Author

Terme, Magali, primary, Ullrich, Evelyn, additional, Aymeric, Laetitia, additional, Meinhardt, Kathrin, additional, Coudert, Jérôme D., additional, Desbois, Mélanie, additional, Ghiringhelli, François, additional, Viaud, Sophie, additional, Ryffel, Bernard, additional, Yagita, Hideo, additional, Chen, Lieping, additional, Mécheri, Salaheddine, additional, Kaplanski, Gilles, additional, Prévost-Blondel, Armelle, additional, Kato, Masashi, additional, Schultze, Joachim L., additional, Tartour, Eric, additional, Kroemer, Guido, additional, Degli-Esposti, Mariapia, additional, Chaput, Nathalie, additional, and Zitvogel, Laurence, additional

Published
2012
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50. IL-18 Induces PD-1–Dependent Immunosuppression in Cancer

Author

Terme, Magali, primary, Ullrich, Evelyn, additional, Aymeric, Laetitia, additional, Meinhardt, Kathrin, additional, Desbois, Mélanie, additional, Delahaye, Nicolas, additional, Viaud, Sophie, additional, Ryffel, Bernard, additional, Yagita, Hideo, additional, Kaplanski, Gilles, additional, Prévost-Blondel, Armelle, additional, Kato, Masashi, additional, Schultze, Joachim L., additional, Tartour, Eric, additional, Kroemer, Guido, additional, Chaput, Nathalie, additional, and Zitvogel, Laurence, additional

Published
2011
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