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1. 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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2. Data from The Polarity and Specificity of Antiviral T Lymphocyte Responses Determine Susceptibility to SARS-CoV-2 Infection in Patients with Cancer and Healthy Individuals

Author

Fahrner, Jean-Eudes, primary, Lahmar, Imran, primary, Goubet, Anne-Gaëlle, primary, Haddad, Yacine, primary, Carrier, Agathe, primary, Mazzenga, Marine, primary, Drubay, Damien, primary, Alves Costa Silva, Carolina, primary, de Sousa, Eric, primary, Thelemaque, Cassandra, primary, Melenotte, Cléa, primary, Dubuisson, Agathe, primary, Geraud, Arthur, primary, Ferrere, Gladys, primary, Birebent, Roxanne, primary, Bigenwald, Camille, primary, Picard, Marion, primary, Cerbone, Luigi, primary, Lérias, Joana R., primary, Laparra, Ariane, primary, Bernard-Tessier, Alice, primary, Kloeckner, Benoît, primary, Gazzano, Marianne, primary, Danlos, François-Xavier, primary, Terrisse, Safae, primary, Pizzato, Eugenie, primary, Flament, Caroline, primary, Ly, Pierre, primary, Tartour, Eric, primary, Benhamouda, Nadine, primary, Meziani, Lydia, primary, Ahmed-Belkacem, Abdelhakim, primary, Miyara, Makoto, primary, Gorochov, Guy, primary, Barlesi, Fabrice, primary, Trubert, Alexandre, primary, Ungar, Benjamin, primary, Estrada, Yeriel, primary, Pradon, Caroline, primary, Gallois, Emmanuelle, primary, Pommeret, Fanny, primary, Colomba, Emeline, primary, Lavaud, Pernelle, primary, Deloger, Marc, primary, Droin, Nathalie, primary, Deutsch, Eric, primary, Gachot, Bertrand, primary, Spano, Jean-Philippe, primary, Merad, Mansouria, primary, Scotté, Florian, primary, Marabelle, Aurélien, primary, Griscelli, Frank, primary, Blay, Jean-Yves, primary, Soria, Jean-Charles, primary, Merad, Miriam, primary, André, Fabrice, primary, Villemonteix, Juliette, primary, Chevalier, Mathieu F., primary, Caillat-Zucman, Sophie, primary, Fenollar, Florence, primary, Guttman-Yassky, Emma, primary, Launay, Odile, primary, Kroemer, Guido, primary, La Scola, Bernard, primary, Maeurer, Markus, primary, Derosa, Lisa, primary, and Zitvogel, Laurence, primary

Published
2023
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3. 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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4. 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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5. Supplementary Data from The Polarity and Specificity of Antiviral T Lymphocyte Responses Determine Susceptibility to SARS-CoV-2 Infection in Patients with Cancer and Healthy Individuals

Author

Fahrner, Jean-Eudes, primary, Lahmar, Imran, primary, Goubet, Anne-Gaëlle, primary, Haddad, Yacine, primary, Carrier, Agathe, primary, Mazzenga, Marine, primary, Drubay, Damien, primary, Alves Costa Silva, Carolina, primary, de Sousa, Eric, primary, Thelemaque, Cassandra, primary, Melenotte, Cléa, primary, Dubuisson, Agathe, primary, Geraud, Arthur, primary, Ferrere, Gladys, primary, Birebent, Roxanne, primary, Bigenwald, Camille, primary, Picard, Marion, primary, Cerbone, Luigi, primary, Lérias, Joana R., primary, Laparra, Ariane, primary, Bernard-Tessier, Alice, primary, Kloeckner, Benoît, primary, Gazzano, Marianne, primary, Danlos, François-Xavier, primary, Terrisse, Safae, primary, Pizzato, Eugenie, primary, Flament, Caroline, primary, Ly, Pierre, primary, Tartour, Eric, primary, Benhamouda, Nadine, primary, Meziani, Lydia, primary, Ahmed-Belkacem, Abdelhakim, primary, Miyara, Makoto, primary, Gorochov, Guy, primary, Barlesi, Fabrice, primary, Trubert, Alexandre, primary, Ungar, Benjamin, primary, Estrada, Yeriel, primary, Pradon, Caroline, primary, Gallois, Emmanuelle, primary, Pommeret, Fanny, primary, Colomba, Emeline, primary, Lavaud, Pernelle, primary, Deloger, Marc, primary, Droin, Nathalie, primary, Deutsch, Eric, primary, Gachot, Bertrand, primary, Spano, Jean-Philippe, primary, Merad, Mansouria, primary, Scotté, Florian, primary, Marabelle, Aurélien, primary, Griscelli, Frank, primary, Blay, Jean-Yves, primary, Soria, Jean-Charles, primary, Merad, Miriam, primary, André, Fabrice, primary, Villemonteix, Juliette, primary, Chevalier, Mathieu F., primary, Caillat-Zucman, Sophie, primary, Fenollar, Florence, primary, Guttman-Yassky, Emma, primary, Launay, Odile, primary, Kroemer, Guido, primary, La Scola, Bernard, primary, Maeurer, Markus, primary, Derosa, Lisa, primary, and Zitvogel, Laurence, primary

Published
2023
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6. Supplementary Figure from The Polarity and Specificity of Antiviral T Lymphocyte Responses Determine Susceptibility to SARS-CoV-2 Infection in Patients with Cancer and Healthy Individuals

Author

Fahrner, Jean-Eudes, primary, Lahmar, Imran, primary, Goubet, Anne-Gaëlle, primary, Haddad, Yacine, primary, Carrier, Agathe, primary, Mazzenga, Marine, primary, Drubay, Damien, primary, Alves Costa Silva, Carolina, primary, de Sousa, Eric, primary, Thelemaque, Cassandra, primary, Melenotte, Cléa, primary, Dubuisson, Agathe, primary, Geraud, Arthur, primary, Ferrere, Gladys, primary, Birebent, Roxanne, primary, Bigenwald, Camille, primary, Picard, Marion, primary, Cerbone, Luigi, primary, Lérias, Joana R., primary, Laparra, Ariane, primary, Bernard-Tessier, Alice, primary, Kloeckner, Benoît, primary, Gazzano, Marianne, primary, Danlos, François-Xavier, primary, Terrisse, Safae, primary, Pizzato, Eugenie, primary, Flament, Caroline, primary, Ly, Pierre, primary, Tartour, Eric, primary, Benhamouda, Nadine, primary, Meziani, Lydia, primary, Ahmed-Belkacem, Abdelhakim, primary, Miyara, Makoto, primary, Gorochov, Guy, primary, Barlesi, Fabrice, primary, Trubert, Alexandre, primary, Ungar, Benjamin, primary, Estrada, Yeriel, primary, Pradon, Caroline, primary, Gallois, Emmanuelle, primary, Pommeret, Fanny, primary, Colomba, Emeline, primary, Lavaud, Pernelle, primary, Deloger, Marc, primary, Droin, Nathalie, primary, Deutsch, Eric, primary, Gachot, Bertrand, primary, Spano, Jean-Philippe, primary, Merad, Mansouria, primary, Scotté, Florian, primary, Marabelle, Aurélien, primary, Griscelli, Frank, primary, Blay, Jean-Yves, primary, Soria, Jean-Charles, primary, Merad, Miriam, primary, André, Fabrice, primary, Villemonteix, Juliette, primary, Chevalier, Mathieu F., primary, Caillat-Zucman, Sophie, primary, Fenollar, Florence, primary, Guttman-Yassky, Emma, primary, Launay, Odile, primary, Kroemer, Guido, primary, La Scola, Bernard, primary, Maeurer, Markus, primary, Derosa, Lisa, primary, and Zitvogel, Laurence, primary

Published
2023
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7. Guidelines for DC preparation and flow cytometry analysis of mouse nonlymphoid tissues

Author

Probst, Hans Christian, Stoitzner, Patrizia, Amon, Lukas, Backer, Ronald A, Brand, Anna, Chen, Jianzhou, Clausen, Björn E, Dieckmann, Sophie, Dudziak, Diana, Heger, Lukas, Hodapp, Katrin, Hornsteiner, Florian, Hovav, Avi-Hai, Jacobi, Lukas, Ji, Xingqi, Kamenjarin, Nadine, Lahl, Katharina, Lahmar, Imran, Lakus, Jelena, Lehmann, Christian H K, Ortner, Daniela, Picard, Marion, Roberti, Maria Paula, Rossnagel, Lukas, Saba, Yasmin, Schalla, Carmen, Schlitzer, Andreas, Schraml, Barbara U, Schütze, Kristian, Seichter, Anna, Seré, Kristin, Seretis, Athanasios, Sopper, Sieghart, Strandt, Helen, Sykora, Martina M, Theobald, Hannah, Tripp, Christoph H, Zitvogel, Laurence, Probst, Hans Christian, Stoitzner, Patrizia, Amon, Lukas, Backer, Ronald A, Brand, Anna, Chen, Jianzhou, Clausen, Björn E, Dieckmann, Sophie, Dudziak, Diana, Heger, Lukas, Hodapp, Katrin, Hornsteiner, Florian, Hovav, Avi-Hai, Jacobi, Lukas, Ji, Xingqi, Kamenjarin, Nadine, Lahl, Katharina, Lahmar, Imran, Lakus, Jelena, Lehmann, Christian H K, Ortner, Daniela, Picard, Marion, Roberti, Maria Paula, Rossnagel, Lukas, Saba, Yasmin, Schalla, Carmen, Schlitzer, Andreas, Schraml, Barbara U, Schütze, Kristian, Seichter, Anna, Seré, Kristin, Seretis, Athanasios, Sopper, Sieghart, Strandt, Helen, Sykora, Martina M, Theobald, Hannah, Tripp, Christoph H, and Zitvogel, Laurence

Abstract

This article is part of the Dendritic Cell Guidelines article series, which provides a collection of state-of-the-art protocols for the preparation, phenotype analysis by flow cytometry, generation, fluorescence microscopy and functional characterization of mouse and human dendritic cells (DC) from lymphoid organs and various nonlymphoid tissues. DC are sentinels of the immune system present in almost every mammalian organ. Since they represent a rare cell population, DC need to be extracted from organs with protocols that are specifically developed for each tissue. This article provides detailed protocols for the preparation of single-cell suspensions from various mouse nonlymphoid tissues, including skin, intestine, lung, kidney, mammary glands, oral mucosa and transplantable tumors. Furthermore, our guidelines include comprehensive protocols for multiplex flow cytometry analysis of DC subsets and feature top tricks for their proper discrimination from other myeloid cells. With this collection, we provide guidelines for in-depth analysis of DC subsets that will advance our understanding of their respective roles in healthy and diseased tissues. While all protocols were written by experienced scientists who routinely use them in their work, this article was also peer-reviewed by leading experts and approved by all coauthors, making it an essential resource for basic and clinical DC immunologists.

Published
2023

8. The Lung Immune Prognostic Index (LIPI) stratifies prognostic groups and correlates with gut microbiota (GM) in patients with advanced renal cell carcinoma (RCC).

Author

Silva, Carolina Alves Costa, primary, Zoppi, Silvia, additional, Reni, Anna, additional, Piccinno, Gianmarco, additional, Lahmar, Imran, additional, Cerbone, Luigi, additional, Carril-Ajuria, Lucía, additional, Colomba, Emeline, additional, Flippot, Ronan, additional, Sow, Cissé, additional, Segata, Nicola, additional, Escudier, Bernard, additional, Zitvogel, Laurence, additional, Albiges, Laurence, additional, and Derosa, Lisa, additional

Published
2023
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9. RBD- specific Th1 responses are associated with vaccine-induced protection against SARS-CoV-2 infection in patients with hematological malignancies

Author

Bigenwald, Camille, primary, Haddad, Yacine, additional, Thelemaque, Cassandra, additional, Carrier, Agathe, additional, Birebent, Roxanne, additional, Ly, Pierre, additional, Flament, Caroline, additional, Lahmar, Imran, additional, de Sousa, Eric, additional, Maeurer, Markus, additional, Miyara, Makoto, additional, Assi, Tarek, additional, Castilla-Llorente, Cristina, additional, Willekens, Christophe, additional, Fayemi, Céline, additional, Lazarovici, Julien, additional, Marabelle, Aurélien, additional, Derosa, Lisa, additional, Ribrag, Vincent, additional, and Zitvogel, Laurence, additional

Published
2023
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10. Guidelines for DC preparation and flow cytometry analysis of mouse nonlymphoid tissues

Author

Probst, Hans Christian, primary, Stoitzner, Patrizia, additional, Amon, Lukas, additional, Backer, Ronald A., additional, Brand, Anna, additional, Chen, Jianzhou, additional, Clausen, Björn E., additional, Dieckmann, Sophie, additional, Dudziak, Diana, additional, Heger, Lukas, additional, Hodapp, Katrin, additional, Hornsteiner, Florian, additional, Hovav, Avi‐Hai, additional, Jacobi, Lukas, additional, Ji, Xingqi, additional, Kamenjarin, Nadine, additional, Lahl, Katharina, additional, Lahmar, Imran, additional, Lakus, Jelena, additional, Lehmann, Christian H. K., additional, Ortner, Daniela, additional, Picard, Marion, additional, Roberti, Maria Paula, additional, Rossnagel, Lukas, additional, Saba, Yasmin, additional, Schalla, Carmen, additional, Schlitzer, Andreas, additional, Schraml, Barbara U., additional, Schütze, Kristian, additional, Seichter, Anna, additional, Seré, Kristin, additional, Seretis, Athanasios, additional, Sopper, Sieghart, additional, Strandt, Helen, additional, Sykora, Martina M., additional, Theobald, Hannah, additional, Tripp, Christoph H., additional, and Zitvogel, Laurence, additional

Published
2022
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11. Le Double Cursus Santé Sciences à l’UFR Santé de Rouen

Author

Dabaj, Ivana, primary, Lahmar, Imran, additional, Gomez, Anaëlle, additional, Barbey, Léo, additional, Verdier, Antonin, additional, Delage, Colombe, additional, Galateau, Eva, additional, Aubert, Raphaël, additional, Gehanno, Alexandre, additional, Schaal, Pauline, additional, Feldmann, Lea, additional, Tebani, Abdellah, additional, Estour, François, additional, and Bekri, Soumeya, additional

Published
2022
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12. 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

13. 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

14. 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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15. 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

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

Author

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

Published
2021
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17. 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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18. Serum soluble MAdCAM-1: A new biomarker for cancer immunotherapy.

Author

Silva, Carolina Alves Costa, Fidelle, Marine, Birebent, Roxanne, Dalban, Cécile, Zoppi, Silvia, Reni, Anna, Rauber, Conrad, Lahmar, Imran, Mallard de La Varende, Anne-Laure, Rioux-Leclercq, Nathalie, Sautès-Fridman, Catherine, Meylan, Maxime, Vano, Yann-Alexandre, Beusenlick, Benoit, Chouaib, Salem, Tantot, Florence, Escudier, Bernard, Zitvogel, Laurence, Derosa, Lisa, and Albiges, Laurence

Published
2023
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19. Cancer induces a stress ileopathy depending on B-adrenergic receptors and promoting dysbiosis that contribute to carcinogenesis

Author

Satoru Yonekura, Safae Terrisse, Carolina Alves Costa Silva, Antoine Lafarge, Valerio Iebba, Gladys Ferrere, Anne-Gaëlle Goubet, Jean-Eudes Fahrner, Imran Lahmar, Kousuke Ueda, Gibrail Mansouri, Eugénie Pizzato, Pierre Ly, Marine Mazzenga, Cassandra Thelemaque, Marine Fidelle, Fanny Jaulin, Jérôme Cartry, Marc Deloger, Marine Aglave, Nathalie Droin, Paule Opolon, Angélique Puget, Fanny Mann, Michel Neunlist, Anne Bessard, Laetitia Aymeric, Tamara Matysiak-Budnik, Jacques Bosq, Paul Hofman, Connie P.M. Duong, Sophie Ugolini, Valentin Quiniou, Sylvie Berrard, Bernhard Ryffel, Oliver Kepp, Guido Kroemer, Bertrand Routy, Leonardo Lordello, Mohamed-Amine Bani, Nicola Segata, Fjodor Yousef Yengej, Hans Clevers, Jean-Yves Scoazec, Edoardo Pasolli, Lisa Derosa, Laurence Zitvogel, Hubrecht Institute for Developmental Biology and Stem Cell Research, Yonekura, Satoru, Terrisse, Safae, Alves Costa Silva, Carolina, Lafarge, Antoine, Iebba, Valerio, Ferrere, Glady, Goubet, Anne-Gaelle, Fahrner, Jean-Eude, 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, Jacque, 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, Han, Scoazec, Jean-Yve, Pasolli, Edoardo, Derosa, Lisa, Zitvogel, Laurence, Institut de Biologie du Développement de Marseille (IBDM), and Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS)

Subjects
metagenomics, bioinformatic, Carcinogenesis, [SDV]Life Sciences [q-bio], microbiome, bioinformatics, Gut dysbiosi, B-adrenergic receptors, Gut dysbiosis, Oncology, epithelial barrier permeability, chemiotherapy, Receptors, Adrenergic, beta, microbiota, carcinogenesis, stress ileopathy, immunotherapy, Dysbiosis, Humans, carcinogenesi, Intestinal Mucosa, metagenomic, B-adrenergic receptor, Signal Transduction
Abstract

Gut dysbiosis has been associated with intestinal and extraintestinal 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. The rapid onset of tumorigenesis induced a burst of REG3γ release by ileal cells, and transient epithelial barrier permeability that culminated in overt and long-lasting dysbiosis dominated by Gram-positive Clostridium species. Pharmacologic blockade of β-adrenergic receptors or genetic deficiency in Adrb2 gene, vancomycin, or cohousing of tumor bearers with tumor-free littermates prevented cancer-induced ileopathy, eventually slowing tumor growth kinetics. Patients with cancer harbor distinct hallmarks of this stress ileopathy dominated by Clostridium species. Hence, stress ileopathy is a corollary disease of extraintestinal malignancies requiring specific therapies. Significance: Whether gut dysbiosis promotes tumorigenesis and how it controls tumor progression remain open questions. We show that 50% of transplantable extraintestinal malignancies triggered a β-adrenergic receptor–dependent ileal mucosa atrophy, associated with increased gut permeability, sustained Clostridium spp.–related dysbiosis, and cancer growth. Vancomycin or propranolol prevented cancer-associated stress ileopathy. This article is highlighted in the In This Issue feature, p. 873

Published
2022

20. Guidelines for DC preparation and flow cytometry analysis of mouse nonlymphoid tissues.

Author

Probst HC, Stoitzner P, Amon L, Backer RA, Brand A, Chen J, Clausen BE, Dieckmann S, Dudziak D, Heger L, Hodapp K, Hornsteiner F, Hovav AH, Jacobi L, Ji X, Kamenjarin N, Lahl K, Lahmar I, Lakus J, Lehmann CHK, Ortner D, Picard M, Roberti MP, Rossnagel L, Saba Y, Schalla C, Schlitzer A, Schraml BU, Schütze K, Seichter A, Seré K, Seretis A, Sopper S, Strandt H, Sykora MM, Theobald H, Tripp CH, and Zitvogel L

Subjects
Animals, Humans, Flow Cytometry, Myeloid Cells, Kidney, Mammals, Dendritic Cells, Skin
Abstract

This article is part of the Dendritic Cell Guidelines article series, which provides a collection of state-of-the-art protocols for the preparation, phenotype analysis by flow cytometry, generation, fluorescence microscopy and functional characterization of mouse and human dendritic cells (DC) from lymphoid organs and various nonlymphoid tissues. DC are sentinels of the immune system present in almost every mammalian organ. Since they represent a rare cell population, DC need to be extracted from organs with protocols that are specifically developed for each tissue. This article provides detailed protocols for the preparation of single-cell suspensions from various mouse nonlymphoid tissues, including skin, intestine, lung, kidney, mammary glands, oral mucosa and transplantable tumors. Furthermore, our guidelines include comprehensive protocols for multiplex flow cytometry analysis of DC subsets and feature top tricks for their proper discrimination from other myeloid cells. With this collection, we provide guidelines for in-depth analysis of DC subsets that will advance our understanding of their respective roles in healthy and diseased tissues. While all protocols were written by experienced scientists who routinely use them in their work, this article was also peer-reviewed by leading experts and approved by all coauthors, making it an essential resource for basic and clinical DC immunologists., (© 2022 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.)

Published
2023
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21. A microbiota-modulated checkpoint directs immunosuppressive intestinal T cells into cancers.

Author

Fidelle M, Rauber C, Alves Costa Silva C, Tian AL, Lahmar I, de La Varende AM, Zhao L, Thelemaque C, Lebhar I, Messaoudene M, Pizzato E, Birebent R, Mbogning Fonkou MD, Zoppi S, Reni A, Dalban C, Leduc M, Ferrere G, Durand S, Ly P, Silvin A, Mulder K, Dutertre CA, Ginhoux F, Yonekura S, Roberti MP, Tidjani-Alou M, Terrisse S, Chen J, Kepp O, Schippers A, Wagner N, Suárez-Gosálvez J, Kobold S, Fahrner JE, Richard C, Bosq J, Lordello L, Vitali G, Galleron N, Quinquis B, Le Chatelier E, Blanchard L, Girard JP, Jarry A, Gervois N, Godefroy E, Labarrière N, Koschny R, Daillère R, Besse B, Truntzer C, Ghiringhelli F, Coatnoan N, Mhanna V, Klatzmann D, Drubay D, Albiges L, Thomas AM, Segata N, Danlos FX, Marabelle A, Routy B, Derosa L, Kroemer G, and Zitvogel L

Subjects
Animals, Humans, Mice, Bacteria immunology, Cell Movement, Fecal Microbiota Transplantation, Interleukin-17 metabolism, Th17 Cells immunology, Gastrointestinal Tract immunology, Gastrointestinal Tract microbiology, Anti-Bacterial Agents adverse effects, Cell Adhesion Molecules metabolism, Drug Resistance, Neoplasm, Gastrointestinal Microbiome immunology, Immune Checkpoint Inhibitors therapeutic use, Immune Tolerance drug effects, Immunologic Surveillance, Integrins metabolism, Mucoproteins metabolism, Neoplasms immunology, Neoplasms therapy
Abstract

Antibiotics (ABX) compromise the efficacy of programmed cell death protein 1 (PD-1) blockade in cancer patients, but the mechanisms underlying their immunosuppressive effects remain unknown. By inducing the down-regulation of mucosal addressin cell adhesion molecule 1 (MAdCAM-1) in the ileum, post-ABX gut recolonization by Enterocloster species drove the emigration of enterotropic α4β7 + CD4 + regulatory T 17 cells into the tumor. These deleterious ABX effects were mimicked by oral gavage of Enterocloster species, by genetic deficiency, or by antibody-mediated neutralization of MAdCAM-1 and its receptor, α4β7 integrin. By contrast, fecal microbiota transplantation or interleukin-17A neutralization prevented ABX-induced immunosuppression. In independent lung, kidney, and bladder cancer patient cohorts, low serum levels of soluble MAdCAM-1 had a negative prognostic impact. Thus, the MAdCAM-1-α4β7 axis constitutes an actionable gut immune checkpoint in cancer immunosurveillance.

Published
2023
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22. [The Double degree in Health and Sciences Curriculum at the Rouen Health UFR: Current situation and perspectives].

Author

Dabaj I, Lahmar I, Gomez A, Barbey L, Verdier A, Delage C, Galateau E, Aubert R, Gehanno A, Schaal P, Feldmann L, Tebani A, Estour F, and Bekri S

Subjects
France, Humans, Students, United States, Curriculum, Faculty
Abstract

The Double degree in Health and Sciences (DCSS) provides an early training in research for future healthcare professionals. The profound transformation of the healthcare system and the advent of new analytical and digital technologies highlight the urgent need to link research to clinical practice. At the international level, especially in the United States, these programs point out the key role of healthcare professionals with both medical and scientific expertise. In France, a DCSS during medical studies was set up in the 2000's. This training is still heterogeneous and is not organized in all Faculties of Health Sciences. The Rouen Faculty of Health Sciences observed in 2016 that the number of students involved in DCSS was very low or even zero, depending on the year. The Rouen Faculty of Health Sciences initiated an institutional support in 2017 that led to the creation of a student mentorship dedicated to DCSS. This mentorship and the institutional leaders of this course have initiated a theoretical and practical training program. The organization of the DCSS of the Rouen Faculty of Health Sciences and the creation of a student mentorship program enabled us to increase the number of candidates interested in the DCSS (from 2 in 2016 to 26 in 2021) and to obtain an institutional recognition of this double major., (© 2022 médecine/sciences – Inserm.)

Published
2022
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23. Cancer Induces a Stress Ileopathy Depending on β-Adrenergic Receptors and Promoting Dysbiosis that Contributes to Carcinogenesis.

Author

Yonekura S, Terrisse S, Alves Costa Silva C, Lafarge A, Iebba V, Ferrere G, Goubet AG, Fahrner JE, Lahmar I, Ueda K, Mansouri G, Pizzato E, Ly P, Mazzenga M, Thelemaque C, Fidelle M, Jaulin F, Cartry J, Deloger M, Aglave M, Droin N, Opolon P, Puget A, Mann F, Neunlist M, Bessard A, Aymeric L, Matysiak-Budnik T, Bosq J, Hofman P, Duong CPM, Ugolini S, Quiniou V, Berrard S, Ryffel B, Kepp O, Kroemer G, Routy B, Lordello L, Bani MA, Segata N, Yengej FY, Clevers H, Scoazec JY, Pasolli E, Derosa L, and Zitvogel L

Subjects
Carcinogenesis pathology, Humans, Intestinal Mucosa pathology, Signal Transduction, Dysbiosis chemically induced, Dysbiosis complications, Dysbiosis pathology, Receptors, Adrenergic, beta
Abstract

Gut dysbiosis has been associated with intestinal and extraintestinal 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. The rapid onset of tumorigenesis induced a burst of REG3γ release by ileal cells, and transient epithelial barrier permeability that culminated in overt and long-lasting dysbiosis dominated by Gram-positive Clostridium species. Pharmacologic blockade of β-adrenergic receptors or genetic deficiency in Adrb2 gene, vancomycin, or cohousing of tumor bearers with tumor-free littermates prevented cancer-induced ileopathy, eventually slowing tumor growth kinetics. Patients with cancer harbor distinct hallmarks of this stress ileopathy dominated by Clostridium species. Hence, stress ileopathy is a corollary disease of extraintestinal malignancies requiring specific therapies., Significance: Whether gut dysbiosis promotes tumorigenesis and how it controls tumor progression remain open questions. We show that 50% of transplantable extraintestinal malignancies triggered a β-adrenergic receptor-dependent ileal mucosa atrophy, associated with increased gut permeability, sustained Clostridium spp.-related dysbiosis, and cancer growth. Vancomycin or propranolol prevented cancer-associated stress ileopathy. This article is highlighted in the In This Issue feature, p. 873., (©2021 American Association for Cancer Research.)

Published
2022
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24. The Polarity and Specificity of Antiviral T Lymphocyte Responses Determine Susceptibility to SARS-CoV-2 Infection in Patients with Cancer and Healthy Individuals.

Author

Fahrner JE, Lahmar I, Goubet AG, Haddad Y, Carrier A, Mazzenga M, Drubay D, Alves Costa Silva C, de Sousa E, Thelemaque C, Melenotte C, Dubuisson A, Geraud A, Ferrere G, Birebent R, Bigenwald C, Picard M, Cerbone L, Lérias JR, Laparra A, Bernard-Tessier A, Kloeckner B, Gazzano M, Danlos FX, Terrisse S, Pizzato E, Flament C, Ly P, Tartour E, Benhamouda N, Meziani L, Ahmed-Belkacem A, Miyara M, Gorochov G, Barlesi F, Trubert A, Ungar B, Estrada Y, Pradon C, Gallois E, Pommeret F, Colomba E, Lavaud P, Deloger M, Droin N, Deutsch E, Gachot B, Spano JP, Merad M, Scotté F, Marabelle A, Griscelli F, Blay JY, Soria JC, Merad M, André F, Villemonteix J, Chevalier MF, Caillat-Zucman S, Fenollar F, Guttman-Yassky E, Launay O, Kroemer G, La Scola B, Maeurer M, Derosa L, and Zitvogel L

Subjects
Antibodies, Neutralizing, Humans, SARS-CoV-2, Spike Glycoprotein, Coronavirus chemistry, Spike Glycoprotein, Coronavirus genetics, Antiviral Restriction Factors immunology, COVID-19 immunology, Neoplasms complications, T-Lymphocytes immunology
Abstract

Vaccination against coronavirus disease 2019 (COVID-19) relies on the in-depth understanding of protective immune responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We characterized the polarity and specificity of memory T cells directed against SARS-CoV-2 viral lysates and peptides to determine correlates with spontaneous, virus-elicited, or vaccine-induced protection against COVID-19 in disease-free and cancer-bearing individuals. A disbalance between type 1 and 2 cytokine release was associated with high susceptibility to COVID-19. Individuals susceptible to infection exhibited a specific deficit in the T helper 1/T cytotoxic 1 (Th1/Tc1) peptide repertoire affecting the receptor binding domain of the spike protein (S1-RBD), a hotspot of viral mutations. Current vaccines triggered Th1/Tc1 responses in only a fraction of all subject categories, more effectively against the original sequence of S1-RBD than that from viral variants. We speculate that the next generation of vaccines should elicit Th1/Tc1 T-cell responses against the S1-RBD domain of emerging viral variants., Significance: This study prospectively analyzed virus-specific T-cell correlates of protection against COVID-19 in healthy and cancer-bearing individuals. A disbalance between Th1/Th2 recall responses conferred susceptibility to COVID-19 in both populations, coinciding with selective defects in Th1 recognition of the receptor binding domain of spike. See related commentary by McGary and Vardhana, p. 892. This article is highlighted in the In This Issue feature, p. 873., (©2022 The Authors; Published by the American Association for Cancer Research.)

Published
2022
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