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37 results on '"Dhainaut, Maxime"'

1. ImmGen at 15

Author

Aguilar, Stephanie Vargas, Aguilar, Oscar, Allan, Rhys, Amir, El Ad David, Angeli, Veronique, Artyomov, Maxim N, Asinovski, Natasha, Astarita, Jilian, Austen, K Frank, Bajpai, Geetika, Barrett, Nora, Baysoy, Alev, Benoist, Christophe, Bellemare-Pelletier, Angelique, Berg, Brad, Best, Adam, Bezman, Natalie, Blair, David, Blander, Julie M, Bogunovic, Milena, Brennan, Patrick, Brenner, Michael, Brown, Brian, Buechler, Matthew, Buenrostro, Jason, Casanova, Maria Acebes, Choi, Kyunghee, Chow, Andrew, Chudnovskiy, Aleksey, Cipoletta, Daniela, Cohen, Nadia, Collins, James J, Colonna, Marco, Cook, Alison, Costello, James, Cremasco, Viviana, Crowl, Ty, Crozat, Karine, Cruse, Richard, D'Angelo, June, Dalod, Marc, Davis, Scott, Demiralp, Cagatay, Deng, Tianda, Desai, Jigar V, Desland, Fiona, Dhainaut, Maxime, Ding, Jiarui, Doedens, Andrew, Dominguez, Claudia, Doran, Graeme, Dress, Regine, Dustin, Michael, Dwyer, Daniel, Dzhagalov, Ivan, Elpek, Kutlu, Ergun, Ayla, Ericson, Jeff, Esomonu, Eunice, Fairfax, Keke, Fletcher, Anne, Frascoli, Michela, Fuchs, Anja, Gainullina, Anastasiia, Gal-Oz, Shani, Gallagher, Michael, Gautier, Emmanuel, Gazit, Roi, Gibbings, Sophie, Giraud, Matthieu, Ginhoux, Florent, Goldrath, Ananda, Gotthardt, Dagmar, Gray, Daniel, Greter, Melanie, Grieshaber-Bouyer, Ricardo, Guilliams, Martin, Haidermota, Sara, Hardy, Randy, Hashimoto, Daigo, Helft, Julie, Hendricks, Deborah, Heng, Tracy, Hill, Jonathan, Hyatt, Gordon, Idoyaga, Juliana, Jakubzick, Claudia, Jarjoura, Jessica, Jepson, Daniel, Jia, Baosen, Jianu, Radu, Johanson, Tim, Jordan, Stefan, Jojic, Vladimir, Kamimura, Yosuke, Kana, Veronica, Kang, Joonsoo, Kapoor, Varun, and Kenigsberg, Ephriam

Subjects
Animals, Gene Expression Regulation, Gene Regulatory Networks, Genomics, History, 21st Century, Immune System, Immunologic Techniques, Mice, Immunological Genome Project, Immunology
Published
2020

2. Spatial CRISPR genomics identifies regulators of the tumor microenvironment

Author

Dhainaut, Maxime, Rose, Samuel A., Akturk, Guray, Wroblewska, Aleksandra, Nielsen, Sebastian R., Park, Eun Sook, Buckup, Mark, Roudko, Vladimir, Pia, Luisanna, Sweeney, Robert, Le Berichel, Jessica, Wilk, C. Matthias, Bektesevic, Anela, Lee, Brian H., Bhardwaj, Nina, Rahman, Adeeb H., Baccarini, Alessia, Gnjatic, Sacha, Pe’er, Dana, Merad, Miriam, and Brown, Brian D.

Published
2022
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3. Tissue-resident macrophages provide a pro-tumorigenic niche to early NSCLC cells

Author

Casanova-Acebes, María, Dalla, Erica, Leader, Andrew M., LeBerichel, Jessica, Nikolic, Jovan, Morales, Blanca M., Brown, Markus, Chang, Christie, Troncoso, Leanna, Chen, Steven T., Sastre-Perona, Ana, Park, Matthew D., Tabachnikova, Alexandra, Dhainaut, Maxime, Hamon, Pauline, Maier, Barbara, and Sawai, Catherine M.

Subjects
Lung cancer, Non-small cell -- Development and progression, Macrophages -- Health aspects, Cancer cells -- Health aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Macrophages have a key role in shaping the tumour microenvironment (TME), tumour immunity and response to immunotherapy, which makes them an important target for cancer treatment.sup.1,2. However, modulating macrophages has proved extremely difficult, as we still lack a complete understanding of the molecular and functional diversity of the tumour macrophage compartment. Macrophages arise from two distinct lineages. Tissue-resident macrophages self-renew locally, independent of adult haematopoiesis.sup.3-5, whereas short-lived monocyte-derived macrophages arise from adult haematopoietic stem cells, and accumulate mostly in inflamed lesions.sup.1. How these macrophage lineages contribute to the TME and cancer progression remains unclear. To explore the diversity of the macrophage compartment in human non-small cell lung carcinoma (NSCLC) lesions, here we performed single-cell RNA sequencing of tumour-associated leukocytes. We identified distinct populations of macrophages that were enriched in human and mouse lung tumours. Using lineage tracing, we discovered that these macrophage populations differ in origin and have a distinct temporal and spatial distribution in the TME. Tissue-resident macrophages accumulate close to tumour cells early during tumour formation to promote epithelial-mesenchymal transition and invasiveness in tumour cells, and they also induce a potent regulatory T cell response that protects tumour cells from adaptive immunity. Depletion of tissue-resident macrophages reduced the numbers and altered the phenotype of regulatory T cells, promoted the accumulation of CD8.sup.+ T cells and reduced tumour invasiveness and growth. During tumour growth, tissue-resident macrophages became redistributed at the periphery of the TME, which becomes dominated by monocyte-derived macrophages in both mouse and human NSCLC. This study identifies the contribution of tissue-resident macrophages to early lung cancer and establishes them as a target for the prevention and treatment of early lung cancer lesions. Single-cell RNA sequencing and imaging of macrophages in human non-small cell lung cancer and in a mouse model of lung adenocarcinoma show that tissue-resident macrophages have a key role in early tumour progression., Author(s): María Casanova-Acebes [sup.1] [sup.2] [sup.3] [sup.19] , Erica Dalla [sup.4] [sup.5] [sup.6] [sup.7] , Andrew M. Leader [sup.1] [sup.2] [sup.3] , Jessica LeBerichel [sup.1] [sup.2] [sup.3] , Jovan Nikolic [...]

Published
2021
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8. Supplementary Data from β-Catenin Activation Promotes Immune Escape and Resistance to Anti–PD-1 Therapy in Hepatocellular Carcinoma

Author

Ruiz de Galarreta, Marina, primary, Bresnahan, Erin, primary, Molina-Sánchez, Pedro, primary, Lindblad, Katherine E., primary, Maier, Barbara, primary, Sia, Daniela, primary, Puigvehi, Marc, primary, Miguela, Verónica, primary, Casanova-Acebes, María, primary, Dhainaut, Maxime, primary, Villacorta-Martin, Carlos, primary, Singhi, Aatur D., primary, Moghe, Akshata, primary, von Felden, Johann, primary, Tal Grinspan, Lauren, primary, Wang, Shuang, primary, Kamphorst, Alice O., primary, Monga, Satdarshan P., primary, Brown, Brian D., primary, Villanueva, Augusto, primary, Llovet, Josep M., primary, Merad, Miriam, primary, and Lujambio, Amaia, primary

Published
2023
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9. Figure S5 from β-Catenin Activation Promotes Immune Escape and Resistance to Anti–PD-1 Therapy in Hepatocellular Carcinoma

Author

Ruiz de Galarreta, Marina, primary, Bresnahan, Erin, primary, Molina-Sánchez, Pedro, primary, Lindblad, Katherine E., primary, Maier, Barbara, primary, Sia, Daniela, primary, Puigvehi, Marc, primary, Miguela, Verónica, primary, Casanova-Acebes, María, primary, Dhainaut, Maxime, primary, Villacorta-Martin, Carlos, primary, Singhi, Aatur D., primary, Moghe, Akshata, primary, von Felden, Johann, primary, Tal Grinspan, Lauren, primary, Wang, Shuang, primary, Kamphorst, Alice O., primary, Monga, Satdarshan P., primary, Brown, Brian D., primary, Villanueva, Augusto, primary, Llovet, Josep M., primary, Merad, Miriam, primary, and Lujambio, Amaia, primary

Published
2023
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10. Data from β-Catenin Activation Promotes Immune Escape and Resistance to Anti–PD-1 Therapy in Hepatocellular Carcinoma

Author

Ruiz de Galarreta, Marina, primary, Bresnahan, Erin, primary, Molina-Sánchez, Pedro, primary, Lindblad, Katherine E., primary, Maier, Barbara, primary, Sia, Daniela, primary, Puigvehi, Marc, primary, Miguela, Verónica, primary, Casanova-Acebes, María, primary, Dhainaut, Maxime, primary, Villacorta-Martin, Carlos, primary, Singhi, Aatur D., primary, Moghe, Akshata, primary, von Felden, Johann, primary, Tal Grinspan, Lauren, primary, Wang, Shuang, primary, Kamphorst, Alice O., primary, Monga, Satdarshan P., primary, Brown, Brian D., primary, Villanueva, Augusto, primary, Llovet, Josep M., primary, Merad, Miriam, primary, and Lujambio, Amaia, primary

Published
2023
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11. Model-Free Error Assessment for Breadth-First Studies, with Applications to Cell-Perturbation Experiments

Author

Loper, Jackson, Barton, Robert, Subramaniam, Meena, Dhainaut, Maxime, and Regier, Jeffrey

Subjects
FOS: Computer and information sciences, 62P10 (Primary) 92C37 (Secondary), Applications (stat.AP), Statistics - Applications
Abstract

We consider high-throughput experiments that take measurements regarding many parameters. Due to resource limitations, ``breadth-first'' high-throughput experiments take only a few independent samples of each parameter, and so it is challenging to assess estimator error. We propose a new model-free method for bounding type S errors in this context, based on a quantity we call the Cross-replicate Sign Error Rate (CSER). The CSER is the expected sign agreement between a fixed set of estimates and estimates based on an independent experimental replicate. To show the CSER can be estimated with enough accuracy to be useful in practice, we develop new improvements to Hoeffding's bounds for sums of bounded random variables, obtaining the tightest bounds that can be obtained from the Chernoff inequality. We apply this method to analyzing measurements from cell-perturbation experiments. Our method reveals that existing error control practices fail to control error at their nominal level in some cases and are needlessly conservative in others. The CSER is easy to estimate, enabling practitioners to detect problems in their experimental designs and identify subsets of parameters with a low proportion of type S errors., Submitted to JRSS-B

Published
2022

16. Perturb-map enables CRISPR genomics with spatial resolution and identifies regulators of tumor immune composition

Author

Dhainaut, Maxime, primary, Rose, Samuel A, additional, Akturk, Guray, additional, Wroblewska, Aleksandra, additional, Park, Eun Sook, additional, Nielsen, Sebastian R, additional, Buckup, Mark, additional, Roudko, Vladimir, additional, Pia, Luisanna, additional, Le Berichel, Jessica, additional, Bektesevic, Anela, additional, Lee, Brian H, additional, Baccarini, Alessia, additional, Bhardwaj, Nina, additional, Rahman, Adeeb H, additional, Gnjatic, Sacha, additional, Pe’er, Dana, additional, Merad, Miriam, additional, and Brown, Brian D, additional

Published
2021
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18. Sampling the host response to SARS-CoV-2 in hospitals under siege

Author

Charney, Alexander W., Simons, Nicole W., Mouskas, Konstantinos, Lepow, Lauren, Cheng, Esther, Le Berichel, Jessica, Chang, Christie, Marvin, Robert, Del Valle, Diane Marie, Calorossi, Sharlene, Lansky, Alona, Walker, Laura, Patel, Manishkumar, Xie, Hui, Yi, Nancy, Yu, Alex, Kang, Gurpawan, Mendoza, Anthony, Liharska, Lora E., Moya, Emily, Hartnett, Matthew, Hatem, Sandra, Wilkins, Lillian, Eaton, Melody, Jamal, Hajra, Tuballes, Kevin, Chen, Steven T., Tabachnikova, Alexandra, Chung, Jonathan, Harris, Jocelyn, Batchelor, Craig, Lacunza, Jose, Yishak, Mahlet, Argueta, Kimberly, Karekar, Neha, Lee, Brian, Kelly, Geoffrey, Geanon, Daniel, Handler, Diana, Leech, John, Stefanos, Hiyab, Dawson, Travis, Scott, Ieisha, Francoeur, Nancy, Johnson, Jessica S., Vaid, Akhil, Glicksberg, Benjamin S., Nadkarni, Girish N., Schadt, Eric E., Gelb, Bruce D., Rahman, Adeeb, Sebra, Robert, Martin, Glenn, Agashe, Charuta, Agrawal, Priyal, Akyatan, Alara, Alesso-Carra, Kasey, Alibo, Eziwoma, Alvarez, Kelvin, Amabile, Angelo, Ascolillo, Steven, Bailey, Rasheed, Begani, Priya, Correra, Paloma Bravo, Brown, Stacey-Ann, Buckup, Mark, Burka, Larissa, Cambron, Lena, Carrara, Gina, Chang, Serena, Chien, Jonathan, Chowdhury, Mashkura, Bozkus, Cansu Cimen, Comella, Phillip, Cosgrove, Dana, Cossarini, Francesca, Cotter, Liam, Dave, Arpit, Dayal, Bheesham, Dhainaut, Maxime, Dornfeld, Rebecca, Dul, Katie, Eber, Nissan, Elaiho, Cordelia, Fabris, Frank, Faith, Jeremiah, Falci, Dominique, Feng, Susie, Fennessy, Brian, Fernandes, Marie, Gangadharan, Sandeep, Grabowska, Joanna, Gyimesi, Gavin, Hamdani, Maha, Herbinet, Manon, Herrera, Elva, Hochman, Arielle, Hoffman, Gabriel E., Hook, Jaime, Horta, Laila, Humblin, Etienne, Karim, Subha, Kim, Jessica, Lebovitch, Dannielle, Lee, Grace, Lee, Gyu Ho, Lee, Jacky, Leventhal, Mike, Lindblad, Katherine, Livanos, Alexandra, Machado, Rosalie, Mahmood, Zafar, Mar, Kelcey, Maskey, Shrisha, Matthews, Paul, Meckel, Katherine, Mehandru, Saurabh, Mercedes, Cynthia, Meyer, Dara, Mollaoglu, Gurkan, Morris, Sarah, Nie, Kai, Nisenholtz, Marjorie, Ofori-Amanfo, George, Onel, Kenan, Ounadjela, Merouane, Patel, Vishwendra, Pruitt, Cassandra, Rathi, Shivani, Redes, Jamie, Reyes-Torres, Ivan, Rodrigues, Alcina, Rodriguez, Alfonso, Roudko, Vladimir, Ruiz, Evelyn, Scalzo, Pearl, Silva, Pedro, Schanoski, Alessandra Soares, Straw, Meghan, Tabachnikova, Sasha, Teague, Collin, Upadhyaya, Bhaskar, Van Der Heide, Verena, Vaninov, Natalie, Wacker, Daniel, Walsh, Hadley, Wilk, C. Matthias, Wilson, Jessica, Wilson, Karen M., Xue, Li, Yeboah, Naa-akomaah, Young, Sabina, Zaks, Nina, Zha, Renyuan, Marron, Thomas, Beckmann, Noam, Kim-Schulze, Seunghee, Gnjatic, Sacha, and Merad, Miriam

Subjects
Siege, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), biology, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Host response, Sampling (statistics), General Medicine, biology.organism_classification, Virology, General Biochemistry, Genetics and Molecular Biology, Pandemic, Medicine, business, Betacoronavirus
Published
2020
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19. β-Catenin Activation Promotes Immune Escape and Resistance to Anti–PD-1 Therapy in Hepatocellular Carcinoma

Author

Ruiz de Galarreta, Marina, primary, Bresnahan, Erin, additional, Molina-Sánchez, Pedro, additional, Lindblad, Katherine E., additional, Maier, Barbara, additional, Sia, Daniela, additional, Puigvehi, Marc, additional, Miguela, Verónica, additional, Casanova-Acebes, María, additional, Dhainaut, Maxime, additional, Villacorta-Martin, Carlos, additional, Singhi, Aatur D., additional, Moghe, Akshata, additional, von Felden, Johann, additional, Tal Grinspan, Lauren, additional, Wang, Shuang, additional, Kamphorst, Alice O., additional, Monga, Satdarshan P., additional, Brown, Brian D., additional, Villanueva, Augusto, additional, Llovet, Josep M., additional, Merad, Miriam, additional, and Lujambio, Amaia, additional

Published
2019
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20. Guidelines for optimized gene knockout using CRISPR/Cas9

Author

Campenhout, Claude Van, primary, Cabochette, Pauline, additional, Veillard, Anne-Clémence, additional, Laczik, Miklos, additional, Zelisko-Schmidt, Agnieszka, additional, Sabatel, Céline, additional, Dhainaut, Maxime, additional, Vanhollebeke, Benoit, additional, Gueydan, Cyril, additional, and Kruys, Véronique, additional

Published
2019
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21. Guidelines for optimized gene knockout using CRISPR/Cas9.

Author

Campenhout, Claude Van, Cabochette, Pauline, Veillard, Anne-Clémence, Laczik, Miklos, Zelisko-Schmidt, Agnieszka, Sabatel, Céline, Dhainaut, Maxime, Vanhollebeke, Benoît, Gueydan, Cyril, Kruys, Véronique, Campenhout, Claude Van, Cabochette, Pauline, Veillard, Anne-Clémence, Laczik, Miklos, Zelisko-Schmidt, Agnieszka, Sabatel, Céline, Dhainaut, Maxime, Vanhollebeke, Benoît, Gueydan, Cyril, and Kruys, Véronique

Abstract

CRISPR/Cas9 technology has evolved as the most powerful approach to generate genetic models both for fundamental and preclinical research. Despite its apparent simplicity, the outcome of a genome-editing experiment can be substantially impacted by technical parameters and biological considerations. Here, we present guidelines and tools to optimize CRISPR/Cas9 genome-targeting efficiency and specificity. The nature of the target locus, the design of the single guide RNA and the choice of the delivery method should all be carefully considered prior to a genome-editing experiment. Different methods can also be used to detect off-target cleavages and decrease the risk of unwanted mutations. Together, these optimized tools and proper controls are essential to the assessment of CRISPR/Cas9 genome-editing experiments., SCOPUS: re.j, info:eu-repo/semantics/published

Published
2019

22. Towards best-practice approaches for CRISPR/Cas9 gene engineering

Author

Van Campenhout, Claude, primary, Cabochette, Pauline, additional, Veillard, Anne-Clémence, additional, Laczik, Miklos, additional, Zelisko-Schmidt, Agnieszka, additional, Sabatel, Céline, additional, Dhainaut, Maxime, additional, Vanhollebeke, Benoit, additional, Gueydan, Cyril, additional, and Kruys, Véronique, additional

Published
2018
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27. Intrinsic and extrinsic control of the proinflammatory CD70/CD27 pathway

Author

Dhainaut, Maxime, Moser, Muriel, Gueydan, Cyril, Goriely, Stanislas, Sansom, David, and Liston, Adrian

Subjects
Inflammation, Inflammation (Pathologie), Système lymphatique, Lymphocytes T, Costimulation, Cellules dendritiques, Lymphatics, T cells, hemic and immune systems, chemical and pharmacologic phenomena, Regulatory T cells, Biologie, Dendritic cells
Abstract

A key step in the development of an adaptive immune response is the activation of naive T cells by dendritic cells (DCs). DCs sample antigens in the periphery and migrate to the lymphoid organs were they provide different signals to T cells: they present antigenic peptides in the context of MHC molecules, express costimulatory or coinhibitory ligands and produce cytokines that influence T cell fate. The integration of these signals will either induce tolerance or lead to the activation and expansion of effector T cells which will mediate the immune response.The costimulatory CD70/CD27 pathway plays important roles in the development of pro-inflammatory Th1 and CTL responses. CD70 expression on DCs has also been described as a molecular switch from tolerance to immunity. Accordingly, its activity is tightly regulated in vivo. The aim of this work was to investigate the mechanisms controlling the expression of CD70 on dendritic cells and CD27 on T lymphocytes.First, we described a cell-extrinsic mechanism of inhibition exerted on DCs by regulatory T cells (Tregs). Indeed, Tregs controlled Th1 priming in vivo and in vitro by downregulating CD70 on DCs. This control involved a transfer of the CD27 receptor to DCs, possibly via the production of CD27-bearing microvesicles by T cells at the immunological synapse. Acquisition of CD27 by DCs induced the internalization of both CD27 and CD70 and probably their lysosomal degradation. As a consequence, DCs were impaired in their ability to efficiently prime Th1 cells. Second, we analyzed CD70 and CD27 expression in the periphery and provided evidence for a cell-intrinsic control of CD27 expression by ectodomain shedding in the gastrointestinal tract.While they efficiently clear infections, inflammatory responses can also be deleterious to the organism. By restraining CD70 expression on DCs, Tregs would promote tolerance and limit inflammation. Interestingly, tolerance is particularly important in the intestines, which are in constant contact with dietary antigens and the commensal microbiota. Accordingly, we propose that a second layer of control of CD27-driven costimulation takes place in the gut :by shedding CD27, T cells would be desensitized for any potential CD70-dependent costimulation.To further investigate the physiological significance of the mechanisms described above, the immune response will be monitored in animals specifically lacking CD27 expression in the Treg population or expressing a nonsheddable CD27 receptor., Doctorat en Sciences, info:eu-repo/semantics/nonPublished

Published
2015

28. In Vivo Interleukin-13-Primed Macrophages Contribute to Reduced Alloantigen-Specific T Cell Activation and Prolong Immunological Survival of Allogeneic Mesenchymal Stem Cell Implants

Author

Hoornaert, Chloé C.J., Verbeeck, Louca, Quarta, Alessandra, De Vocht, Nathalie, Lemmens, Evi, Goossens, Herman, van der linden, Annemie, Roobrouck, Valerie V.D., Verfaillie, Catherine, Hendrix, Sven, Moser, Muriel, Luyckx, Evi, Berneman, Zwi Nisan, Ponsaerts, Peter, Reekmans, Kristien, Dhainaut, Maxime, Guglielmetti, Caroline, Le Blon, Debbie, Dooley, Dearbhaile, Fransen, Erik, Daans, Jasmijn, Hoornaert, Chloé C.J., Verbeeck, Louca, Quarta, Alessandra, De Vocht, Nathalie, Lemmens, Evi, Goossens, Herman, van der linden, Annemie, Roobrouck, Valerie V.D., Verfaillie, Catherine, Hendrix, Sven, Moser, Muriel, Luyckx, Evi, Berneman, Zwi Nisan, Ponsaerts, Peter, Reekmans, Kristien, Dhainaut, Maxime, Guglielmetti, Caroline, Le Blon, Debbie, Dooley, Dearbhaile, Fransen, Erik, and Daans, Jasmijn

Abstract

Transplantation of mesenchymal stem cells (MSCs) into injured or diseased tissue—for the in situ delivery of a wide variety of MSC-secreted therapeutic proteins—is an emerging approach for the modulation of the clinical course of several diseases and traumata. From an emergency point-of-view, allogeneic MSCs have numerous advantages over patient-specific autologous MSCs since “off-the-shelf” cell preparations could be readily available for instant therapeutic intervention following acute injury. Although we confirmed the in vitro immunomodulatory capacity of allogeneic MSCs on antigen-presenting cells with standard coculture experiments, allogeneic MSC grafts were irrevocably rejected by the host's immune system upon either intramuscular or intracerebral transplantation. In an attempt to modulate MSC allograft rejection in vivo, we transduced MSCs with an interleukin-13 (IL13)-expressing lentiviral vector. Our data clearly indicate that prolonged survival of IL13-expressing allogeneic MSC grafts in muscle tissue coincided with the induction of an alternatively activated macrophage phenotype in vivo and a reduced number of alloantigen-reactive IFNγ- and/or IL2-producing CD8+ T cells compared to nonmodified allografts. Similarly, intracerebral IL13-expressing MSC allografts also exhibited prolonged survival and induction of an alternatively activated macrophage phenotype, although a peripheral T cell component was absent. In summary, this study demonstrates that both innate and adaptive immune responses are effectively modulated in vivo by locally secreted IL13, ultimately resulting in prolonged MSC allograft survival in both muscle and brain tissue. Stem Cells 2016;34:1971–1984., SCOPUS: ar.j, FLWOA, info:eu-repo/semantics/published

Published
2016

29. In Vivo Interleukin-13-Primed Macrophages Contribute to Reduced Alloantigen-Specific T Cell Activation and Prolong Immunological Survival of Allogeneic Mesenchymal Stem Cell Implants

Author

Hoornaert, Chloé J., primary, Luyckx, Evi, additional, Reekmans, Kristien, additional, Dhainaut, Maxime, additional, Guglielmetti, Caroline, additional, Le Blon, Debbie, additional, Dooley, Dearbhaile, additional, Fransen, Erik, additional, Daans, Jasmijn, additional, Verbeeck, Louca, additional, Quarta, Alessandra, additional, De Vocht, Nathalie, additional, Lemmens, Evi, additional, Goossens, Herman, additional, Van der Linden, Annemie, additional, Roobrouck, Valerie D., additional, Verfaillie, Catherine, additional, Hendrix, Sven, additional, Moser, Muriel, additional, Berneman, Zwi N., additional, and Ponsaerts, Peter, additional

Published
2016
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30. Intrinsic and extrinsic control of the proinflammatory CD70/CD27 pathway

Author

Moser, Muriel, Gueydan, Cyril, Goriely, Stanislas, Sansom, David, Liston, Adrian, Dhainaut, Maxime, Moser, Muriel, Gueydan, Cyril, Goriely, Stanislas, Sansom, David, Liston, Adrian, and Dhainaut, Maxime

Abstract

A key step in the development of an adaptive immune response is the activation of naive T cells by dendritic cells (DCs). DCs sample antigens in the periphery and migrate to the lymphoid organs were they provide different signals to T cells: they present antigenic peptides in the context of MHC molecules, express costimulatory or coinhibitory ligands and produce cytokines that influence T cell fate. The integration of these signals will either induce tolerance or lead to the activation and expansion of effector T cells which will mediate the immune response.The costimulatory CD70/CD27 pathway plays important roles in the development of pro-inflammatory Th1 and CTL responses. CD70 expression on DCs has also been described as a molecular switch from tolerance to immunity. Accordingly, its activity is tightly regulated in vivo. The aim of this work was to investigate the mechanisms controlling the expression of CD70 on dendritic cells and CD27 on T lymphocytes.First, we described a cell-extrinsic mechanism of inhibition exerted on DCs by regulatory T cells (Tregs). Indeed, Tregs controlled Th1 priming in vivo and in vitro by downregulating CD70 on DCs. This control involved a transfer of the CD27 receptor to DCs, possibly via the production of CD27-bearing microvesicles by T cells at the immunological synapse. Acquisition of CD27 by DCs induced the internalization of both CD27 and CD70 and probably their lysosomal degradation. As a consequence, DCs were impaired in their ability to efficiently prime Th1 cells. Second, we analyzed CD70 and CD27 expression in the periphery and provided evidence for a cell-intrinsic control of CD27 expression by ectodomain shedding in the gastrointestinal tract.While they efficiently clear infections, inflammatory responses can also be deleterious to the organism. By restraining CD70 expression on DCs, Tregs would promote tolerance and limit inflammation. Interestingly, tolerance is particularly important in the intestines, which, Doctorat en Sciences, info:eu-repo/semantics/nonPublished

Published
2015

31. Thymus‐derived regulatory T cells restrain pro‐inflammatory Th1 responses by downregulating CD 70 on dendritic cells

Author

Dhainaut, Maxime, primary, Coquerelle, Caroline, additional, Uzureau, Sophie, additional, Denoeud, Julie, additional, Acolty, Valérie, additional, Oldenhove, Guillaume, additional, Galuppo, Adrien, additional, Sparwasser, Tim, additional, Thielemans, Kris, additional, Pays, Etienne, additional, Yagita, Hideo, additional, Borst, Jannie, additional, and Moser, Muriel, additional

Published
2015
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33. Regulation of immune reactivity by intercellular transfer

Author

Dhainaut, Maxime, Moser, Muriel, Dhainaut, Maxime, and Moser, Muriel

Abstract

It was recently proposed that T lymphocytes, which closely interact with APCs, can extract surface molecules from the presenting cells when they dissociate. These observations question the classical view of discrete interactions between phenotypically defined cell populations. In this review, we summarize some reports suggesting that membrane exchange at the immune synapse can be a vector for intercellular communication and envisage some consequences on the biology of T cells. © 2014 Dhainaut and Moser., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2014

37. NOTCH1 drives sexually dimorphic immune responses in hepatocellular carcinoma.

Author

Lindblad KE, Donne R, Liebling I, Barcena-Varela M, Lozano A, Ruiz de Galarreta M, Dhainaut M, Param NJ, Giotti B, Cappuyns S, Kodama T, Wang Y, Kamphorst AO, Tsankov AM, and Lujambio A

Abstract

Hepatocellular carcinoma presents strong sexual dimorphism, being 2-3 times more frequent in males than in females; however, the role of sex in response to immunotherapies in HCC remains unknown. We demonstrate that NOTCH1, an understudied oncogene in HCC, elicits sexually dimorphic anti-tumor immunity and response to FDA-approved immunotherapies. Surprisingly, males harboring NOTCH1-driven tumors displayed enhanced anti-tumor immune responses, which, in mice, were mediated by dendritic and T cells. Conversely, females harboring NOTCH1-driven tumors presented immune evasion and resistance to immunotherapies through a defect in DC-mediated priming and activation of CD8+ T cells in mice, which was restored therapeutically with CD40 agonism. Mechanistically, the sexually dimorphic immunity was mediated by genes in the sex chromosomes but not by sex hormones. Together, our study unravels an unexpected association between NOTCH1 and sex in cancer immunity and highlights the potential of restoring the DC-CD8+ T cell axis with CD40 agonism to improve outcomes.

Published
2024
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