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132 results on '"Tugues, Sonia"'

1. ROCK1/2 signaling contributes to corticosteroid-refractory acute graft-versus-host disease

Author

Maas-Bauer, Kristina, Stell, Anna-Verena, Yan, Kai-Li, de Vega, Enrique, Vinnakota, Janaki Manoja, Unger, Susanne, Núñez, Nicolas, Norona, Johana, Talvard-Balland, Nana, Koßmann, Stefanie, Schwan, Carsten, Miething, Cornelius, Martens, Uta S., Shoumariyeh, Khalid, Nestor, Rosa P., Duquesne, Sandra, Hanke, Kathrin, Rackiewicz, Michal, Hu, Zehan, El Khawanky, Nadia, Taromi, Sanaz, Andrlova, Hana, Faraidun, Hemin, Walter, Stefanie, Pfeifer, Dietmar, Follo, Marie, Waldschmidt, Johannes, Melchinger, Wolfgang, Rassner, Michael, Wehr, Claudia, Schmitt-Graeff, Annette, Halbach, Sebastian, Liao, James, Häcker, Georg, Brummer, Tilman, Dengjel, Joern, Andrieux, Geoffroy, Grosse, Robert, Tugues, Sonia, Blazar, Bruce R., Becher, Burkhard, Boerries, Melanie, and Zeiser, Robert

Published
2024
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2. IL-23 stabilizes an effector Treg cell program in the tumor microenvironment

Author

Wertheimer, Tobias, Zwicky, Pascale, Rindlisbacher, Lukas, Sparano, Colin, Vermeer, Marijne, de Melo, Bruno Marcel Silva, Haftmann, Claudia, Rückert, Tamina, Sethi, Aakriti, Schärli, Stefanie, Huber, Anna, Ingelfinger, Florian, Xu, Caroline, Kim, Daehong, Häne, Philipp, Fonseca da Silva, André, Muschaweckh, Andreas, Nunez, Nicolas, Krishnarajah, Sinduya, Köhler, Natalie, Zeiser, Robert, Oukka, Mohamed, Korn, Thomas, Tugues, Sonia, and Becher, Burkhard

Published
2024
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5. Single-cell profiling of immune system alterations in lymphoid, barrier and solid tissues in aged mice

Author

Krishnarajah, Sinduya, Ingelfinger, Florian, Friebel, Ekaterina, Cansever, Dilay, Amorim, Ana, Andreadou, Myrto, Bamert, David, Litscher, Gioana, Lutz, Mirjam, Mayoux, Maud, Mundt, Sarah, Ridder, Frederike, Sparano, Colin, Stifter, Sebastian Anton, Ulutekin, Can, Unger, Susanne, Vermeer, Marijne, Zwicky, Pascale, Greter, Melanie, Tugues, Sonia, De Feo, Donatella, and Becher, Burkhard

Published
2022
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6. Immunization against poly- N -acetylglucosamine reduces neutrophil activation and GVHD while sparing microbial diversity

Author

Hülsdünker, Jan, Thomas, Oliver S., Haring, Eileen, Unger, Susanne, Núñez, Nicolás Gonzalo, Tugues, Sonia, Gao, Zhan, Duquesne, Sandra, Cywes-Bentley, Colette, Oyardi, Ozlem, Kirschnek, Susanne, Schmitt-Graeff, Annette, Pabst, Oliver, Koenecke, Christian, Duyster, Justus, Apostolova, Petya, Blaser, Martin J., Becher, Burkhard, Pier, Gerald B., Häcker, Georg, and Zeiser, Robert

Published
2019

7. Intratumoral IL-12 delivery empowers CAR-T cell immunotherapy in a pre-clinical model of glioblastoma

Author

Agliardi, Giulia, Liuzzi, Anna Rita, Hotblack, Alastair, De Feo, Donatella, Núñez, Nicolás, Stowe, Cassandra L., Friebel, Ekaterina, Nannini, Francesco, Rindlisbacher, Lukas, Roberts, Thomas A., Ramasawmy, Rajiv, Williams, Iwan P., Siow, Bernard M., Lythgoe, Mark F., Kalber, Tammy L., Quezada, Sergio A., Pule, Martin A., Tugues, Sonia, Straathof, Karin, and Becher, Burkhard

Published
2021
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8. NKG2D-mediated detection of metabolically stressed hepatocytes by innate-like T cells is essential for initiation of NASH and fibrosis

Author

Marinović, Sonja, primary, Lenartić, Maja, additional, Mladenić, Karlo, additional, Šestan, Marko, additional, Kavazović, Inga, additional, Benić, Ante, additional, Krapić, Mia, additional, Rindlisbacher, Lukas, additional, Cokarić Brdov̌ak, Maja, additional, Sparano, Colin, additional, Litscher, Gioana, additional, Turk Wensveen, Tamara, additional, Mikolašević, Ivana, additional, Fǔkar Čupić, Dora, additional, Bilić-Zulle, Lidija, additional, Steinle, Aleksander, additional, Waisman, Ari, additional, Hayday, Adrian, additional, Tugues, Sonia, additional, Becher, Burkhard, additional, Polić, Bojan, additional, and Wensveen, Felix M., additional

Published
2023
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9. Sorafenib promotes graft-versus-leukemia activity in mice and humans through IL-15 production in FLT3-ITD-mutant leukemia cells

Author

Mathew, Nimitha R, Baumgartner, Francis, Braun, Lukas, O'Sullivan, David, Thomas, Simone, Waterhouse, Miguel, Müller, Tony A, Hanke, Kathrin, Taromi, Sanaz, Apostolova, Petya, Illert, Anna L, Melchinger, Wolfgang, Duquesne, Sandra, Schmitt-Graeff, Annette, Osswald, Lena, Yan, Kai-Li, Weber, Arnim, Tugues, Sonia, Spath, Sabine, Pfeifer, Dietmar, Follo, Marie, Claus, Rainer, Lübbert, Michael, Rummelt, Christoph, Bertz, Hartmut, Wäsch, Ralph, Haag, Johanna, Schmidts, Andrea, Schultheiss, Michael, Bettinger, Dominik, Thimme, Robert, Ullrich, Evelyn, Tanriver, Yakup, Vuong, Giang Lam, Arnold, Renate, Hemmati, Philipp, Wolf, Dominik, Ditschkowski, Markus, Jilg, Cordula, Wilhelm, Konrad, Leiber, Christian, Gerull, Sabine, Halter, Jörg, Lengerke, Claudia, Pabst, Thomas, Schroeder, Thomas, Kobbe, Guido, Rösler, Wolf, Doostkam, Soroush, Meckel, Stephan, Stabla, Kathleen, Metzelder, Stephan K, Halbach, Sebastian, Brummer, Tilman, Hu, Zehan, Dengjel, Joern, Hackanson, Björn, Schmid, Christoph, Holtick, Udo, Scheid, Christof, Spyridonidis, Alexandros, Stölzel, Friedrich, Ordemann, Rainer, Müller, Lutz P, Sicre-de-Fontbrune, Flore, Ihorst, Gabriele, Kuball, Jürgen, Ehlert, Jan E, Feger, Daniel, Wagner, Eva-Maria, Cahn, Jean-Yves, Schnell, Jacqueline, Kuchenbauer, Florian, Bunjes, Donald, Chakraverty, Ronjon, Richardson, Simon, Gill, Saar, Kröger, Nicolaus, Ayuk, Francis, Vago, Luca, Ciceri, Fabio, Müller, Antonia M, Kondo, Takeshi, Teshima, Takanori, Klaeger, Susan, Kuster, Bernhard, Weisdorf, Daniel, van der Velden, Walter, Dörfel, Daniela, Bethge, Wolfgang, Hilgendorf, Inken, Hochhaus, Andreas, Andrieux, Geoffroy, Börries, Melanie, Busch, Hauke, Magenau, John, Reddy, Pavan, Labopin, Myriam, Antin, Joseph H, Henden, Andrea S, Hill, Geoffrey R, Kennedy, Glen A, Bar, Merav, Sarma, Anita, McLornan, Donal, Mufti, Ghulam, Oran, Betul, Rezvani, Katayoun, Shah, Omid, Negrin, Robert S, Nagler, Arnon, Prinz, Marco, Burchert, Andreas, Neubauer, Andreas, Beelen, Dietrich, Mackensen, Andreas, von Bubnoff, Nikolas, Herr, Wolfgang, Becher, Burkhard, Socié, Gerard, Caligiuri, Michael A, Ruggiero, Eliana, Bonini, Chiara, Häcker, Georg, Duyster, Justus, Finke, Jürgen, Pearce, Erika, Blazar, Bruce R, and Zeiser, Robert

Subjects
Interleukin-15 -- Health aspects, Gene mutation -- Health aspects, Sorafenib -- Patient outcomes, Gene expression -- Health aspects, Acute myelocytic leukemia -- Genetic aspects -- Development and progression -- Drug therapy, Biological sciences, Health
Abstract

Individuals with acute myeloid leukemia (AML) harboring an internal tandem duplication (ITD) in the gene encoding Fms-related tyrosine kinase 3 (FLT3) who relapse after allogeneic hematopoietic cell transplantation (allo-HCT) have a 1-year survival rate below 20%. We observed that sorafenib, a multitargeted tyrosine kinase inhibitor, increased IL-15 production by FLT3-ITD[sup.+] leukemia cells. This synergized with the allogeneic CD8[sup.+] T cell response, leading to long-term survival in six mouse models of FLT3-ITD[sup.+] AML. Sorafenib-related IL-15 production caused an increase in CD8[sup.+]CD107a[sup.+]IFN-[gamma][sup.+] T cells with features of longevity (high levels of Bcl-2 and reduced PD-1 levels), which eradicated leukemia in secondary recipients. Mechanistically, sorafenib reduced expression of the transcription factor ATF4, thereby blocking negative regulation of interferon regulatory factor 7 (IRF7) activation, which enhanced IL-15 transcription. Both IRF7 knockdown and ATF4 overexpression in leukemia cells antagonized sorafenib-induced IL-15 production in vitro. Human FLT3-ITD[sup.+] AML cells obtained from sorafenib responders following sorafenib therapy showed increased levels of IL-15, phosphorylated IRF7, and a transcriptionally active IRF7 chromatin state. The mitochondrial spare respiratory capacity and glycolytic capacity of CD8[sup.+] T cells increased upon sorafenib treatment in sorafenib responders but not in nonresponders. Our findings indicate that the synergism of T cells and sorafenib is mediated via reduced ATF4 expression, causing activation of the IRF7-IL-15 axis in leukemia cells and thereby leading to metabolic reprogramming of leukemia-reactive T cells in humans. Therefore, sorafenib treatment has the potential to contribute to an immune-mediated cure of FLT3-ITD-mutant AML relapse, an otherwise fatal complication after allo-HCT., Author(s): Nimitha R Mathew [1, 2]; Francis Baumgartner [1]; Lukas Braun [1]; David O'Sullivan [3]; Simone Thomas [4]; Miguel Waterhouse [1]; Tony A Müller [1]; Kathrin Hanke [1, 2]; Sanaz [...]

Published
2018
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13. IL-23 stabilizes an effector Tregcell program in the tumor microenvironment

Author

Wertheimer, Tobias, Zwicky, Pascale, Rindlisbacher, Lukas, Sparano, Colin, Vermeer, Marijne, de Melo, Bruno Marcel Silva, Haftmann, Claudia, Rückert, Tamina, Sethi, Aakriti, Schärli, Stefanie, Huber, Anna, Ingelfinger, Florian, Xu, Caroline, Kim, Daehong, Häne, Philipp, Fonseca da Silva, André, Muschaweckh, Andreas, Nunez, Nicolas, Krishnarajah, Sinduya, Köhler, Natalie, Zeiser, Robert, Oukka, Mohamed, Korn, Thomas, Tugues, Sonia, and Becher, Burkhard

Abstract

Interleukin-23 (IL-23) is a proinflammatory cytokine mainly produced by myeloid cells that promotes tumor growth in various preclinical cancer models and correlates with adverse outcomes. However, as to how IL-23 fuels tumor growth is unclear. Here, we found tumor-associated macrophages to be the main source of IL-23 in mouse and human tumor microenvironments. Among IL-23-sensing cells, we identified a subset of tumor-infiltrating regulatory T (Treg) cells that display a highly suppressive phenotype across mouse and human tumors. The use of three preclinical models of solid cancer in combination with genetic ablation of Il23rin Tregcells revealed that they are responsible for the tumor-promoting effect of IL-23. Mechanistically, we found that IL-23 sensing represents a crucial signal driving the maintenance and stabilization of effector Tregcells involving the transcription factor Foxp3. Our data support that targeting the IL-23/IL-23R axis in cancer may represent a means of eliciting antitumor immunity.

Published
2024
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14. Azathioprine therapy induces selective NK cell depletion and IFN-γ deficiency predisposing to herpesvirus reactivation

Author

Ingelfinger, Florian, primary, Sparano, Colin, additional, Bamert, David, additional, Reyes-Leiva, David, additional, Sethi, Aakriti, additional, Rindlisbacher, Lukas, additional, Zwicky, Pascale, additional, Kreutmair, Stefanie, additional, Widmer, Corinne C., additional, Mundt, Sarah, additional, Cortés-Vicente, Elena, additional, Tugues, Sonia, additional, Becher, Burkhard, additional, and Schreiner, Bettina, additional

Published
2023
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16. Embryonic and neonatal waves generate distinct populations of hepatic ILC1s

Author

Sparano, Colin, primary, Solís-Sayago, Darío, additional, Vijaykumar, Anjali, additional, Rickenbach, Chiara, additional, Vermeer, Marijne, additional, Ingelfinger, Florian, additional, Litscher, Gioana, additional, Fonseca, André, additional, Mussak, Caroline, additional, Mayoux, Maud, additional, Friedrich, Christin, additional, Nombela-Arrieta, César, additional, Gasteiger, Georg, additional, Becher, Burkhard, additional, and Tugues, Sonia, additional

Published
2022
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17. Azathioprine therapy induces selective NK cell depletion and IFN-γ deficiency predisposing to herpesvirus reactivation

Author

Ingelfinger, Florian, Sparano, Colin, Bamert, David, Reyes-Leiva, David, Sethi, Aakriti, Rindlisbacher, Lukas, Zwicky, Pascale, Kreutmair, Stefanie, Widmer, Corinne C, Mundt, Sarah, Cortés-Vicente, Elena, Tugues, Sonia, Becher, Burkhard, Schreiner, Bettina, University of Zurich, Becher, Burkhard, and Schreiner, Bettina

Subjects
2403 Immunology, Immunology, 2723 Immunology and Allergy, 570 Life sciences, biology, Immunology and Allergy, 610 Medicine & health, 10263 Institute of Experimental Immunology, 10040 Clinic for Neurology
Abstract

Azathioprine is a widely prescribed drug for patients with chronic inflammatory diseases such as myasthenia gravis or organ transplant recipients. Azathioprine exerts immunosuppressive effects by inhibiting intracellular purine synthesis and reducing the numbers of circulating B and T lymphocytes. Case reports indicate increased risk for serious infections that can occur despite regular measurements of lymphocyte counts during azathioprine therapy.We sought to comprehensively investigate therapy-associated patient risks and the underlying immune dysfunction of azathioprine use.Peripheral blood leukocytes were analyzed using single-cell mass and spectral flow cytometry to detect specific effects of azathioprine use on the systemic immune signature. Therapy-associated clinical features were analyzed in 2 independent cohorts of myasthenia gravis patients.Azathioprine therapy selectively induced pronounced CD56Our study highlights the risk of development of adverse events during azathioprine therapy and suggests that natural killer cell monitoring could be valuable in clinical practice.

Published
2022
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19. HRG Inhibits Tumor Growth and Metastasis by Inducing Macrophage Polarization and Vessel Normalization through Downregulation of PlGF

Author

Rolny, Charlotte, Mazzone, Massimiliano, Tugues, Sònia, Laoui, Damya, Johansson, Irja, Coulon, Cathy, Squadrito, Mario Leonardo, Segura, Inmaculada, Li, Xiujuan, Knevels, Ellen, Costa, Sandra, Vinckier, Stefan, Dresselaer, Tom, Åkerud, Peter, De Mol, Maria, Salomäki, Henriikka, Phillipson, Mia, Wyns, Sabine, Larsson, Erik, Buysschaert, Ian, Botling, Johan, Himmelreich, Uwe, Van Ginderachter, Jo A., De Palma, Michele, Dewerchin, Mieke, Claesson-Welsh, Lena, and Carmeliet, Peter

Published
2011
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20. Single-cell profiling of immune system alterations in lymphoid, barrier and solid tissues in aged mice

Author

Krishnarajah, Sinduya, primary, Ingelfinger, Florian, additional, Friebel, Ekaterina, additional, Cansever, Dilay, additional, Amorim, Ana, additional, Andreadou, Myrto, additional, Bamert, David, additional, Litscher, Gioana, additional, Lutz, Mirjam, additional, Mayoux, Maud, additional, Mundt, Sarah, additional, Ridder, Frederike, additional, Sparano, Colin, additional, Stifter, Sebastian Anton, additional, Ulutekin, Can, additional, Unger, Susanne, additional, Vermeer, Marijne, additional, Zwicky, Pascale, additional, Greter, Melanie, additional, Tugues, Sonia, additional, De Feo, Donatella, additional, and Becher, Burkhard, additional

Published
2021
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22. Tumor endothelial cell up-regulation of IDO1 is an immunosuppressive feed-back mechanism that reduces the response to CD40-stimulating immunotherapy

Author

Georganaki, Maria, Ramachandran, Mohanraj, Tuit, Sander, Nunez, Nicolas Gonzalo, Karampatzakis, Alexandros, Fotaki, Grammatiki, van Hooren, Luuk, Huang, Hua, Lugano, Roberta, Ulas, Thomas, Kaunisto, Aura, Holland, Eric C., Ellmark, Peter, Mangsbo, Sara, Schultze, Joachim, Essand, Magnus, Tugues, Sonia, Dimberg, Anna, Georganaki, Maria, Ramachandran, Mohanraj, Tuit, Sander, Nunez, Nicolas Gonzalo, Karampatzakis, Alexandros, Fotaki, Grammatiki, van Hooren, Luuk, Huang, Hua, Lugano, Roberta, Ulas, Thomas, Kaunisto, Aura, Holland, Eric C., Ellmark, Peter, Mangsbo, Sara, Schultze, Joachim, Essand, Magnus, Tugues, Sonia, and Dimberg, Anna

Abstract

CD40-stimulating immunotherapy can elicit potent anti-tumor responses by activating dendritic cells and enhancing T-cell priming. Tumor vessels orchestrate T-cell recruitment during immune response, but the effect of CD40-stimulating immunotherapy on tumor endothelial cells has not been evaluated. Here, we have investigated how tumor endothelial cells transcriptionally respond to CD40-stimulating immunotherapy by isolating tumor endothelial cells from agonistic CD40 mAb- or isotype-treated mice bearing B16-F10 melanoma, and performing RNA-sequencing. Gene set enrichment analysis revealed that agonistic CD40 mAb therapy increased interferon (IFN)-related responses in tumor endothelial cells, including up-regulation of the immunosuppressive enzyme Indoleamine 2, 3-Dioxygenase 1 (IDO1). IDO1 was predominantly expressed in endothelial cells within the tumor microenvironment, and its expression in tumor endothelium was positively correlated to T-cell infiltration and to increased intratumoral expression of IFN gamma. In vitro, endothelial cells up-regulated IDO1 in response to T-cell-derived IFN gamma, but not in response to CD40-stimulation. Combining agonistic CD40 mAb therapy with the IDO1 inhibitor epacadostat delayed tumor growth in B16-F10 melanoma, associated with increased activation of tumor-infiltrating T-cells. Hereby, we show that the tumor endothelial cells up-regulate IDO1 upon CD40-stimulating immunotherapy in response to increased IFN gamma-secretion by T-cells, revealing a novel immunosuppressive feedback mechanism whereby tumor vessels limit T-cell activation.

Published
2020
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23. The Interplay Between Innate Lymphoid Cells and the Tumor Microenvironment

Author

Ducimetière, Laura, Vermeer, Marijne, and Tugues, Sonia

Subjects
lcsh:Immunologic diseases. Allergy, immune modulation, Immunology, innate lymphoid cells, Cell Communication, Review, Immunity, Innate, Lymphocyte Subsets, crosstalk, Immunomodulation, body regions, Cell Movement, Neoplasms, Immunology and Allergy, Animals, Humans, tumor microenvironment, Tumor Escape, Disease Susceptibility, skin and connective tissue diseases, lcsh:RC581-607, immune evasion
Abstract

The multifaceted roles of Innate Lymphoid Cells (ILC) have been widely interrogated in tumor immunity. Whereas, Natural Killer (NK) cells possess undisputable tumor-suppressive properties across multiple types of cancer, the other ILC family members can either promote or inhibit tumor growth depending on the environmental conditions. The differential effects of ILCs on tumor outcome have been attributed to the high degree of heterogeneity and plasticity within the ILC family members. However, it is now becoming clear that ILCs responses are shaped by their dynamic crosstalk with the different components of the tumor microenvironment (TME). In this review, we will give insights into the molecular and cellular players of the ILCs-TME interactions and we will discuss how we can use this knowledge to successfully harness the activity of ILCs for anticancer therapies.

Published
2019

24. IMMU-16. INTRA-TUMOURAL IL-12 DELIVERY ENABLES CAR T-CELL IMMUNOTHERAPY FOR HIGH-GRADE GLIOMA

Author

Agliardi, Giulia, primary, Liuzzi, Anna Rita, additional, Hotblack, Alastair, additional, De Feo, Donatella, additional, Núñez, Nicolás, additional, Friebel, Ekaterina, additional, Nannini, Francesco, additional, Roberts, Thomas, additional, Ramasawmy, Rajiv, additional, Stowe, Cassandra, additional, Williams, Iwan, additional, Siow, Bernard, additional, Lythgoe, Mark, additional, Kalber, Tammy, additional, Quezada, Sergio, additional, Pule, Martin, additional, Tugues, Sonia, additional, Becher, Burkhard, additional, and Straathof, Karin, additional

Published
2020
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25. Abstract 2646: CD39+PD-1+CD8+ T cells mediate metastatic dormancy in breast cancer

Author

de Lara, Paulino Tallón, primary, Cuadrado, Héctor Castañón, additional, Vermeer, Marijne, additional, Núñez, Nicolás, additional, Urdínez, Joaquín, additional, Cecconi, Virginia, additional, Attar, Farkhondeh Movahedian, additional, Glarner, Isabelle, additional, Hiltbrunner, Stefanie, additional, Tugues, Sonia, additional, Becher, Burkhard, additional, and van den Broek, Maries, additional

Published
2020
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26. Conventional NK cells and tissue-resident ILC1s join forces to control liver metastasis

Author

Ducimetière, Laura, primary, Lucchiari, Giulia, additional, Litscher, Gioana, additional, Nater, Marc, additional, Heeb, Laura, additional, Nuñez, Nicolás Gonzalo, additional, Wyss, Laura, additional, Burri, Dominik, additional, Vermeer, Marijne, additional, Gschwend, Julia, additional, Moor, Andreas E., additional, Becher, Burkhard, additional, van den Broek, Maries, additional, and Tugues, Sonia, additional

Published
2020
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27. Single-Cell Mapping of Human Brain Cancer Reveals Tumor-Specific Instruction of Tissue-Invading Leukocytes

Author

Friebel, Ekaterina, primary, Kapolou, Konstantina, additional, Unger, Susanne, additional, Núñez, Nicolás Gonzalo, additional, Utz, Sebastian, additional, Rushing, Elisabeth Jane, additional, Regli, Luca, additional, Weller, Michael, additional, Greter, Melanie, additional, Tugues, Sonia, additional, Neidert, Marian Christoph, additional, and Becher, Burkhard, additional

Published
2020
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28. Single cell mapping of human brain tumors reveals tumor-specific education of tissue-invading leukocytes.

Author

Friebel, Ekaterina, primary, Kapolou, Konstantina, additional, Unger, Susanne, additional, Nunez, Nicolas, additional, Utz, Sebastian, additional, Rushing, Elisabeth Jane, additional, Regli, Luca, additional, Weller, Michael, additional, Greter, Melanie, additional, Tugues, Sonia, additional, Neidert, Marian Christoph, additional, and Becher, Burkhard, additional

Published
2020
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29. Tumor endothelial cell up-regulation of IDO1 is an immunosuppressive feed-back mechanism that reduces the response to CD40-stimulating immunotherapy

Author

Georganaki, Maria, primary, Ramachandran, Mohanraj, additional, Tuit, Sander, additional, Núñez, Nicolás Gonzalo, additional, Karampatzakis, Alexandros, additional, Fotaki, Grammatiki, additional, van Hooren, Luuk, additional, Huang, Hua, additional, Lugano, Roberta, additional, Ulas, Thomas, additional, Kaunisto, Aura, additional, Holland, Eric C, additional, Ellmark, Peter, additional, Mangsbo, Sara M, additional, Schultze, Joachim, additional, Essand, Magnus, additional, Tugues, Sonia, additional, and Dimberg, Anna, additional

Published
2020
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30. Vaccination Against Poly-N-Acetylglucosamine Decreases Neutrophil Activation and Gvhd While Maintaining Microbial Diversity

Author

Haring, Eileen, primary, Hülsdünker, Jan, additional, Thomas, Oliver, additional, Unger, Susanne, additional, Núñez, Nicolás, additional, Tugues, Sonia, additional, Duquesne, Sandra, additional, Cywes-Bentley, Colette, additional, Oyardi, Özlem, additional, Ghao, Zhan, additional, Kirschnek, Susanne, additional, Schmitt-Graeff, Dr., additional, Pabst, Oliver, additional, Koenecke, Christian, additional, Duyster, Justus, additional, Apostolova, Petya, additional, Blaser, Martin, additional, Becher, Burkhard, additional, Pier, Gerald, additional, Häcker, Georg, additional, and Zeiser, Robert, additional

Published
2019
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32. Immunization against poly--acetylglucosamine reduces neutrophil activation and GVHD while sparing microbial diversity

Author

Hülsdünker, Jan, Thomas, Oliver S, Haring, Eileen, Unger, Susanne, Gonzalo Núñez, Nicolás, Tugues, Sonia, Gao, Zhan, Duquesne, Sandra, Cywes-Bentley, Colette, Oyardi, Ozlem, Kirschnek, Susanne, Schmitt-Graeff, Annette, Pabst, Oliver, Koenecke, Christian, Duyster, Justus, Apostolova, Petya, Blaser, Martin J, Becher, Burkhard, Pier, Gerald B, Häcker, Georg, Zeiser, Robert, University of Zurich, and Zeiser, Robert

Subjects
1000 Multidisciplinary, 570 Life sciences, biology, 610 Medicine & health, 10263 Institute of Experimental Immunology
Published
2019

33. Graft-versus-host disease, but not graft-versus-leukemia immunity, is mediated by GM-CSF–licensed myeloid cells

Author

Tugues, Sonia, Amorim, Ana, Spath, Sabine, Martin-Blondel, Guillaume, Schreiner, Bettina, De Feo, Donatella, Lutz, Mirjam, Guscetti, Franco, Apostolova, Petya, Haftmann, Claudia, Hasselblatt, Peter, Núñez, Nicolás Gonzalo, Hottiger, Michael O, van den Broek, Maries, Manz, Markus G, Zeiser, Robert, Becher, Burkhard, University of Zurich, and Becher, Burkhard

Subjects
10032 Clinic for Oncology and Hematology, 570 Life sciences, biology, 10184 Institute of Veterinary Pathology, 2700 General Medicine, General Medicine, 10263 Institute of Experimental Immunology, 10226 Department of Molecular Mechanisms of Disease, 10040 Clinic for Neurology
Published
2018

34. Erratum : Sorafenib promotes graft-versus-leukemia activity in mice and humans through IL-15 production in FLT3-ITD-mutant leukemia cells

Author

Mathew, Nimitha R, Baumgartner, Francis, Braun, Lukas, O'Sullivan, David, Thomas, Simone, Waterhouse, Miguel, Müller, Tony A, Hanke, Kathrin, Taromi, Sanaz, Apostolova, Petya, Illert, Anna L, Melchinger, Wolfgang, Duquesne, Sandra, Schmitt-Graeff, Annette, Osswald, Lena, Yan, Kai-Li, Weber, Arnim, Tugues, Sonia, Spath, Sabine, Pfeifer, Dietmar, Follo, Marie, Claus, Rainer, Lübbert, Michael, Rummelt, Christoph, Bertz, Hartmut, Wäsch, Ralph, Haag, Johanna, Schmidts, Andrea, Schultheiss, Michael, Bettinger, Dominik, Thimme, Robert, Ullrich, Evelyn, Tanriver, Yakup, Vuong, Giang Lam, Arnold, Renate, Hemmati, Philipp, Wolf, Dominik, Ditschkowski, Markus, Jilg, Cordula, Wilhelm, Konrad, Leiber, Christian, Gerull, Sabine, Halter, Jörg, Lengerke, Claudia, Pabst, Thomas, Schroeder, Thomas, Kobbe, Guido, Rösler, Wolf, Doostkam, Soroush, Meckel, Stephan, Stabla, Kathleen, Metzelder, Stephan K, Halbach, Sebastian, Brummer, Tilman, Hu, Zehan, Dengjel, Joern, Hackanson, Björn, Schmid, Christoph, Holtick, Udo, Scheid, Christof, Spyridonidis, Alexandros, Stölzel, Friedrich, Ordemann, Rainer, Müller, Lutz P, Sicre-de-Fontbrune, Flore, Ihorst, Gabriele, Kuball, Jürgen, Ehlert, Jan E, Feger, Daniel, Wagner, Eva-Maria, Cahn, Jean-Yves, Schnell, Jacqueline, Kuchenbauer, Florian, Bunjes, Donald, Chakraverty, Ronjon, Richardson, Simon, Gill, Saar, Kröger, Nicolaus, Ayuk, Francis, Vago, Luca, Ciceri, Fabio, Müller, Antonia M, Kondo, Takeshi, Teshima, Takanori, Klaeger, Susan, Kuster, Bernhard, Kim, Dennis Dong Hwan, Weisdorf, Daniel, van der Velden, Walter, Dörfel, Daniela, Bethge, Wolfgang, Hilgendorf, Inken, Hochhaus, Andreas, Andrieux, Geoffroy, Börries, Melanie, Busch, Hauke, Magenau, John, Reddy, Pavan, Labopin, Myriam, Antin, Joseph H, Henden, Andrea S, Hill, Geoffrey R, Kennedy, Glen A, Bar, Merav, Sarma, Anita, McLornan, Donal, Mufti, Ghulam, Oran, Betul, Rezvani, Katayoun, Shah, Omid, Negrin, Robert S, Nagler, Arnon, Prinz, Marco, Burchert, Andreas, Neubauer, Andreas, Beelen, Dietrich, Mackensen, Andreas, von Bubnoff, Nikolas, Herr, Wolfgang, Becher, Burkhard, Socié, Gerard, Caligiuri, Michael A, Ruggiero, Eliana, Bonini, Chiara, Häcker, Georg, Duyster, Justus, Finke, Jürgen, Pearce, Erika, Blazar, Bruce R, and Zeiser, Robert

Abstract

This corrects the article DOI: 10.1038/nm.4484.

Published
2018

36. Graft-versus-host disease, but not graft-versus-leukemia immunity, is mediated by GM-CSF–licensed myeloid cells

Author

Tugues, Sonia, primary, Amorim, Ana, additional, Spath, Sabine, additional, Martin-Blondel, Guillaume, additional, Schreiner, Bettina, additional, De Feo, Donatella, additional, Lutz, Mirjam, additional, Guscetti, Franco, additional, Apostolova, Petya, additional, Haftmann, Claudia, additional, Hasselblatt, Peter, additional, Núñez, Nicolas G., additional, Hottiger, Michael O., additional, van den Broek, Maries, additional, Manz, Markus G., additional, Zeiser, Robert, additional, and Becher, Burkhard, additional

Published
2018
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37. Erratum: Sorafenib promotes graft-versus-leukemia activity in mice and humans through IL-15 production in FLT3-ITD-mutant leukemia cells

Author

CTI Kuball, MS Hematologie, Cancer, Regenerative Medicine and Stem Cells, Infection & Immunity, Mathew, Nimitha R, Baumgartner, Francis, Braun, Lukas, O'Sullivan, David, Thomas, Simone, Waterhouse, Miguel, Müller, Tony A, Hanke, Kathrin, Taromi, Sanaz, Apostolova, Petya, Illert, Anna L, Melchinger, Wolfgang, Duquesne, Sandra, Schmitt-Graeff, Annette, Osswald, Lena, Yan, Kai-Li, Weber, Arnim, Tugues, Sonia, Spath, Sabine, Pfeifer, Dietmar, Follo, Marie, Claus, Rainer, Lübbert, Michael, Rummelt, Christoph, Bertz, Hartmut, Wäsch, Ralph, Haag, Johanna, Schmidts, Andrea, Schultheiss, Michael, Bettinger, Dominik, Thimme, Robert, Ullrich, Evelyn, Tanriver, Yakup, Vuong, Giang Lam, Arnold, Renate, Hemmati, Philipp, Wolf, Dominik, Ditschkowski, Markus, Jilg, Cordula, Wilhelm, Konrad, Leiber, Christian, Gerull, Sabine, Halter, Jörg, Lengerke, Claudia, Pabst, Thomas, Schroeder, Thomas, Kobbe, Guido, Rösler, Wolf, Doostkam, Soroush, Meckel, Stephan, Stabla, Kathleen, Metzelder, Stephan K, Halbach, Sebastian, Brummer, Tilman, Hu, Zehan, Dengjel, Joern, Hackanson, Björn, Schmid, Christoph, Holtick, Udo, Scheid, Christof, Spyridonidis, Alexandros, Stölzel, Friedrich, Ordemann, Rainer, Müller, Lutz P, Sicre-de-Fontbrune, Flore, Ihorst, Gabriele, Kuball, Jürgen, Ehlert, Jan E, Feger, Daniel, Wagner, Eva-Maria, Cahn, Jean-Yves, Schnell, Jacqueline, Kuchenbauer, Florian, Bunjes, Donald, Chakraverty, Ronjon, Richardson, Simon, Gill, Saar, Kröger, Nicolaus, Ayuk, Francis, Vago, Luca, Ciceri, Fabio, Müller, Antonia M, Kondo, Takeshi, Teshima, Takanori, Klaeger, Susan, Kuster, Bernhard, Kim, Dennis Dong Hwan, Weisdorf, Daniel, van der Velden, Walter, Dörfel, Daniela, Bethge, Wolfgang, Hilgendorf, Inken, Hochhaus, Andreas, Andrieux, Geoffroy, Börries, Melanie, Busch, Hauke, Magenau, John, Reddy, Pavan, Labopin, Myriam, Antin, Joseph H, Henden, Andrea S, Hill, Geoffrey R, Kennedy, Glen A, Bar, Merav, Sarma, Anita, McLornan, Donal, Mufti, Ghulam, Oran, Betul, Rezvani, Katayoun, Shah, Omid, Negrin, Robert S, Nagler, Arnon, Prinz, Marco, Burchert, Andreas, Neubauer, Andreas, Beelen, Dietrich, Mackensen, Andreas, von Bubnoff, Nikolas, Herr, Wolfgang, Becher, Burkhard, Socié, Gerard, Caligiuri, Michael A, Ruggiero, Eliana, Bonini, Chiara, Häcker, Georg, Duyster, Justus, Finke, Jürgen, Pearce, Erika, Blazar, Bruce R, Zeiser, Robert, CTI Kuball, MS Hematologie, Cancer, Regenerative Medicine and Stem Cells, Infection & Immunity, Mathew, Nimitha R, Baumgartner, Francis, Braun, Lukas, O'Sullivan, David, Thomas, Simone, Waterhouse, Miguel, Müller, Tony A, Hanke, Kathrin, Taromi, Sanaz, Apostolova, Petya, Illert, Anna L, Melchinger, Wolfgang, Duquesne, Sandra, Schmitt-Graeff, Annette, Osswald, Lena, Yan, Kai-Li, Weber, Arnim, Tugues, Sonia, Spath, Sabine, Pfeifer, Dietmar, Follo, Marie, Claus, Rainer, Lübbert, Michael, Rummelt, Christoph, Bertz, Hartmut, Wäsch, Ralph, Haag, Johanna, Schmidts, Andrea, Schultheiss, Michael, Bettinger, Dominik, Thimme, Robert, Ullrich, Evelyn, Tanriver, Yakup, Vuong, Giang Lam, Arnold, Renate, Hemmati, Philipp, Wolf, Dominik, Ditschkowski, Markus, Jilg, Cordula, Wilhelm, Konrad, Leiber, Christian, Gerull, Sabine, Halter, Jörg, Lengerke, Claudia, Pabst, Thomas, Schroeder, Thomas, Kobbe, Guido, Rösler, Wolf, Doostkam, Soroush, Meckel, Stephan, Stabla, Kathleen, Metzelder, Stephan K, Halbach, Sebastian, Brummer, Tilman, Hu, Zehan, Dengjel, Joern, Hackanson, Björn, Schmid, Christoph, Holtick, Udo, Scheid, Christof, Spyridonidis, Alexandros, Stölzel, Friedrich, Ordemann, Rainer, Müller, Lutz P, Sicre-de-Fontbrune, Flore, Ihorst, Gabriele, Kuball, Jürgen, Ehlert, Jan E, Feger, Daniel, Wagner, Eva-Maria, Cahn, Jean-Yves, Schnell, Jacqueline, Kuchenbauer, Florian, Bunjes, Donald, Chakraverty, Ronjon, Richardson, Simon, Gill, Saar, Kröger, Nicolaus, Ayuk, Francis, Vago, Luca, Ciceri, Fabio, Müller, Antonia M, Kondo, Takeshi, Teshima, Takanori, Klaeger, Susan, Kuster, Bernhard, Kim, Dennis Dong Hwan, Weisdorf, Daniel, van der Velden, Walter, Dörfel, Daniela, Bethge, Wolfgang, Hilgendorf, Inken, Hochhaus, Andreas, Andrieux, Geoffroy, Börries, Melanie, Busch, Hauke, Magenau, John, Reddy, Pavan, Labopin, Myriam, Antin, Joseph H, Henden, Andrea S, Hill, Geoffrey R, Kennedy, Glen A, Bar, Merav, Sarma, Anita, McLornan, Donal, Mufti, Ghulam, Oran, Betul, Rezvani, Katayoun, Shah, Omid, Negrin, Robert S, Nagler, Arnon, Prinz, Marco, Burchert, Andreas, Neubauer, Andreas, Beelen, Dietrich, Mackensen, Andreas, von Bubnoff, Nikolas, Herr, Wolfgang, Becher, Burkhard, Socié, Gerard, Caligiuri, Michael A, Ruggiero, Eliana, Bonini, Chiara, Häcker, Georg, Duyster, Justus, Finke, Jürgen, Pearce, Erika, Blazar, Bruce R, and Zeiser, Robert

Published
2018

38. Sorafenib promotes graft-versus-leukemia activity in mice and humans through IL-15 production in FLT3-ITD-mutant leukemia cells

Author

Mathew, Nimitha R., Baumgartner, Francis, Braun, Lukas, O'Sullivan, David, Thomas, Simone, Waterhouse, Miguel, Mueller, Tony A., Hanke, Kathrin, Taromi, Sanaz, Apostolova, Petya, Illert, Anna L., Melchinger, Wolfgang, Duquesne, Sandra, Schmitt-Graeff, Annette, Osswald, Lena, Yan, Kai-Li, Weber, Arnim, Tugues, Sonia, Spath, Sabine, Pfeifer, Dietmar, Follo, Marie, Claus, Rainer, Luebbert, Michael, Rummelt, Christoph, Bertz, Hartmut, Waesch, Ralph, Haag, Johanna, Schmidts, Andrea, Schultheiss, Michael, Bettinger, Dominik, Thimme, Robert, Ullrich, Evelyn, Tanriver, Yakup, Vuong, Giang Lam, Arnold, Renate, Hemmati, Philipp, Wolf, Dominik, Ditschkowski, Markus, Jilg, Cordula, Wilhelm, Konrad, Leiber, Christian, Gerull, Sabine, Halter, Joerg, Lengerke, Claudia, Pabst, Thomas, Schroeder, Thomas, Kobbe, Guido, Roesler, Wolf, Doostkam, Soroush, Meckel, Stephan, Stabla, Kathleen, Metzelder, Stephan K., Halbach, Sebastian, Brummer, Tilman, Hu, Zehan, Dengjel, Joern, Hackanson, Bjoern, Schmid, Christoph, Holtick, Udo, Scheid, Christof, Spyridonidis, Alexandros, Stoelzel, Friedrich, Ordemann, Rainer, Mueller, Lutz P., Sicre-de-Fontbrune, Flore, Ihorst, Gabriele, Kuball, Juergen, Ehlert, Jan E., Feger, Daniel, Wagner, Eva-Maria, Cahn, Jean-Yves, Schnell, Jacqueline, Kuchenbauer, Florian, Bunjes, Donald, Chakraverty, Ronjon, Richardson, Simon, Gill, Saar, Kroeger, Nicolaus, Ayuk, Francis, Vago, Luca, Ciceri, Fabio, Mueller, Antonia M., Kondo, Takeshi, Teshima, Takanori, Klaeger, Susan, Kuster, Bernhard, Kim, Dennis (Dong Hwan), Weisdorf, Daniel, van der Velden, Walter, Doerfel, Daniela, Bethge, Wolfgang, Hilgendorf, Inken, Hochhaus, Andreas, Andrieux, Geoffroy, Boerries, Melanie, Busch, Hauke, Magenau, John, Reddy, Pavan, Labopin, Myriam, Antin, Joseph H., Henden, Andrea S., Hill, Geoffrey R., Kennedy, Glen A., Bar, Merav, Sarma, Anita, McLornan, Donal, Mufti, Ghulam, Oran, Betul, Rezvani, Katayoun, Shah, Omid, Negrin, Robert S., Nagler, Arnon, Prinz, Marco, Burchert, Andreas, Neubauer, Andreas, Beelen, Dietrich, Mackensen, Andreas, von Bubnoff, Nikolas, Herr, Wolfgang, Becher, Burkhard, Socie, Gerard, Caligiuri, Michael A., Ruggiero, Eliana, Bonini, Chiara, Haecker, Georg, Duyster, Justus, Finke, Juergen, Pearce, Erika, Blazar, Bruce R., Zeiser, Robert, Mathew, Nimitha R., Baumgartner, Francis, Braun, Lukas, O'Sullivan, David, Thomas, Simone, Waterhouse, Miguel, Mueller, Tony A., Hanke, Kathrin, Taromi, Sanaz, Apostolova, Petya, Illert, Anna L., Melchinger, Wolfgang, Duquesne, Sandra, Schmitt-Graeff, Annette, Osswald, Lena, Yan, Kai-Li, Weber, Arnim, Tugues, Sonia, Spath, Sabine, Pfeifer, Dietmar, Follo, Marie, Claus, Rainer, Luebbert, Michael, Rummelt, Christoph, Bertz, Hartmut, Waesch, Ralph, Haag, Johanna, Schmidts, Andrea, Schultheiss, Michael, Bettinger, Dominik, Thimme, Robert, Ullrich, Evelyn, Tanriver, Yakup, Vuong, Giang Lam, Arnold, Renate, Hemmati, Philipp, Wolf, Dominik, Ditschkowski, Markus, Jilg, Cordula, Wilhelm, Konrad, Leiber, Christian, Gerull, Sabine, Halter, Joerg, Lengerke, Claudia, Pabst, Thomas, Schroeder, Thomas, Kobbe, Guido, Roesler, Wolf, Doostkam, Soroush, Meckel, Stephan, Stabla, Kathleen, Metzelder, Stephan K., Halbach, Sebastian, Brummer, Tilman, Hu, Zehan, Dengjel, Joern, Hackanson, Bjoern, Schmid, Christoph, Holtick, Udo, Scheid, Christof, Spyridonidis, Alexandros, Stoelzel, Friedrich, Ordemann, Rainer, Mueller, Lutz P., Sicre-de-Fontbrune, Flore, Ihorst, Gabriele, Kuball, Juergen, Ehlert, Jan E., Feger, Daniel, Wagner, Eva-Maria, Cahn, Jean-Yves, Schnell, Jacqueline, Kuchenbauer, Florian, Bunjes, Donald, Chakraverty, Ronjon, Richardson, Simon, Gill, Saar, Kroeger, Nicolaus, Ayuk, Francis, Vago, Luca, Ciceri, Fabio, Mueller, Antonia M., Kondo, Takeshi, Teshima, Takanori, Klaeger, Susan, Kuster, Bernhard, Kim, Dennis (Dong Hwan), Weisdorf, Daniel, van der Velden, Walter, Doerfel, Daniela, Bethge, Wolfgang, Hilgendorf, Inken, Hochhaus, Andreas, Andrieux, Geoffroy, Boerries, Melanie, Busch, Hauke, Magenau, John, Reddy, Pavan, Labopin, Myriam, Antin, Joseph H., Henden, Andrea S., Hill, Geoffrey R., Kennedy, Glen A., Bar, Merav, Sarma, Anita, McLornan, Donal, Mufti, Ghulam, Oran, Betul, Rezvani, Katayoun, Shah, Omid, Negrin, Robert S., Nagler, Arnon, Prinz, Marco, Burchert, Andreas, Neubauer, Andreas, Beelen, Dietrich, Mackensen, Andreas, von Bubnoff, Nikolas, Herr, Wolfgang, Becher, Burkhard, Socie, Gerard, Caligiuri, Michael A., Ruggiero, Eliana, Bonini, Chiara, Haecker, Georg, Duyster, Justus, Finke, Juergen, Pearce, Erika, Blazar, Bruce R., and Zeiser, Robert

Abstract

Individuals with acute myeloid leukemia (AML) harboring an internal tandem duplication (ITD) in the gene encoding Fms-related tyrosine kinase 3 (FLT3) who relapse after allogeneic hematopoietic cell transplantation (allo-HCT) have a 1-year survival rate below 20%. We observed that sorafenib, a multitargeted tyrosine kinase inhibitor, increased IL-15 production by FLT3-ITD+ leukemia cells. This synergized with the allogeneic CD8(+) T cell response, leading to long-term survival in six mouse models of FLT3-ITD+ AML. Sorafenib-related IL-15 production caused an increase in CD8(+) CD107a(+) IFN-gamma(+) T cells with features of longevity (high levels of Bcl-2 and reduced PD-1 levels), which eradicated leukemia in secondary recipients. Mechanistically, sorafenib reduced expression of the transcription factor ATF4, thereby blocking negative regulation of interferon regulatory factor 7 (IRF7) activation, which enhanced IL-15 transcription. Both IRF7 knockdown and ATF4 overexpression in leukemia cells antagonized sorafenib-induced IL-15 production in vitro. Human FLT3-ITD+ AML cells obtained from sorafenib responders following sorafenib therapy showed increased levels of IL-15, phosphorylated IRF7, and a transcriptionally active IRF7 chromatin state. The mitochondrial spare respiratory capacity and glycolytic capacity of CD8(+) T cells increased upon sorafenib treatment in sorafenib responders but not in nonresponders. Our findings indicate that the synergism of T cells and sorafenib is mediated via reduced ATF4 expression, causing activation of the IRF7-IL-15 axis in leukemia cells and thereby leading to metabolic reprogramming of leukemia-reactive T cells in humans. Therefore, sorafenib treatment has the potential to contribute to an immune-mediated cure of FLT3-ITD-mutant AML relapse, an otherwise fatal complication after allo-HCT.

Published
2018

40. Tissue microenvironment dictates the fate and tumor-suppressive function of type 3 ILCs

Author

Nussbaum, Kathrin; https://orcid.org/0000-0002-1870-4861, Burkhard, Sara H, Ohs, Isabel, Mair, Florian; https://orcid.org/0000-0001-6732-5449, Klose, Christoph S N, Arnold, Sebastian J, Diefenbach, Andreas, Tugues, Sonia, Becher, Burkhard; https://orcid.org/0000-0002-1541-7867, Nussbaum, Kathrin; https://orcid.org/0000-0002-1870-4861, Burkhard, Sara H, Ohs, Isabel, Mair, Florian; https://orcid.org/0000-0001-6732-5449, Klose, Christoph S N, Arnold, Sebastian J, Diefenbach, Andreas, Tugues, Sonia, and Becher, Burkhard; https://orcid.org/0000-0002-1541-7867

Abstract

Innate lymphoid cells (ILCs) have been classified into "functional subsets" according to their transcription factor and cytokine profiles. Although cytokines, such as IL-12 and IL-23, have been shown to shape plasticity of ILCs, little is known about how the tissue microenvironment influences the plasticity, phenotype, and function of these cells. Here, we show clearly demarcated tissue specifications of Rorc-dependent ILCs across lymphoid and nonlymphoid organs. Although intestinal Rorc fate map-positive (Rorc(fm+)) ILCs show a clear ILC3 phenotype, lymphoid tissue-derived Rorc(fm+) ILCs acquire an natural killer (NK) cell/ILC1-like phenotype. By adoptively transferring Rorc(fm+) ILCs into recipient mice, we show that ILCs distribute among various organs and phenotypically adapt to the tissue environment they invade. When investigating their functional properties, we found that only lymphoid-tissue resident Rorc(fm+) ILCs can suppress tumor growth, whereas intestinal Rorc(fm-) ILC1s or NK cells fail to inhibit tumor progression. We thus propose that the tissue microenvironment, combined with ontogeny, provides the specific function, whereas the phenotype is insufficient to predict the functional properties of ILCs.

Published
2017

44. Histidine-rich glycoprotein blocks collagen-binding integrins and adhesion of endothelial cells through low-affinity interaction with alpha 2 integrin

Author

Roche, Francis, Sipilä, Kalle, Honjo, Satoshi, Staffan, Johansson, Tugues, Sonia, Heino, Jyrki, Claesson-Welsh, Lena, Roche, Francis, Sipilä, Kalle, Honjo, Satoshi, Staffan, Johansson, Tugues, Sonia, Heino, Jyrki, and Claesson-Welsh, Lena

Abstract

The plasma protein histidine-rich glycoprotein (HRG) affects the morphology and function of both endothelial cells (ECs) and monocytes/macrophages in cancer. Here, we examined the mechanism of action of HRG's effect on ECs. HRG suppressed adhesion, spreading and migration of ECs specifically on collagen I (COL I) whereas ECs seeded on other extracellular matrix proteins were insensitive to HRG. HRG did not bind specifically to COL I or to the α-integrin binding site on collagen, GFOGER. Furthermore, HRG's inhibition of EC adhesion was not dependent upon heparan sulfate (HS) moieties as heparitinase-treated ECs remained sensitive to HRG. C2C12 cells expressing α2 integrin, the major collagen-binding α-integrin subunit in ECs, showed increased binding of HRG compared with wild type C2C12 cells lacking the α2 subunit. Recombinant α2 I-domain protein bound HRG and to a higher extent when in active conformation. However, the α2 I-domain bound weakly to HRG compared with COL I and the purified α2β1 ectodomain complex failed to retain HRG. We conclude that HRG binds to α2 integrin through low-affinity interactions in a HS-independent manner, thereby blocking EC-adhesion to COL I.

Published
2015
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45. Tetraspanin CD63 Promotes Vascular Endothelial Growth Factor Receptor 2-beta 1 Integrin Complex Formation, Thereby Regulating Activation and Downstream Signaling in Endothelial Cells in Vitro and in Vivo

Author

Tugues, Sonia, Honjo, Satoshi, König, Christian, Padhan, Narendra, Kroon, Jeffrey, Gualandi, Laura, Li, Xiujuan, Barkefors, Irmeli, Thijssen, Victor L., Griffioen, Arjan W., Claesson-Welsh, Lena, Tugues, Sonia, Honjo, Satoshi, König, Christian, Padhan, Narendra, Kroon, Jeffrey, Gualandi, Laura, Li, Xiujuan, Barkefors, Irmeli, Thijssen, Victor L., Griffioen, Arjan W., and Claesson-Welsh, Lena

Abstract

CD63 is a member of the transmembrane-4 glycoprotein superfamily (tetraspanins) implicated in the regulation of membrane protein trafficking, leukocyte recruitment, and adhesion processes. We have investigated the involvement of CD63 in endothelial cell (EC) signaling downstream of beta 1 integrin and VEGF. We report that silencing of CD63 in primary ECs arrested capillary sprouting and tube formation in vitro because of impaired adhesion and migration of ECs. Mechanistically, CD63 associated with both beta 1 integrin and the main VEGF receptor on ECs, VEGFR2. Our data suggest that CD63 serves to bridge between beta 1 integrin and VEGFR2 because CD63 silencing disrupted VEGFR2-beta 1 integrin complex formation identified using proximity ligation assays. Signaling downstream of beta 1 integrin and VEGFR2 was attenuated in CD63-silenced cells, although their cell surface expression levels remained unaffected. CD63 was furthermore required for efficient internalization of VEGFR2 in response to VEGF. Importantly, systemic delivery of VEGF failed to potently induce VEGFR2 phosphorylation and downstream signaling in CD63-deficient mouse lungs. Taken together, our findings demonstrate a previously unrecognized role for CD63 in coordinated integrin and receptor tyrosine kinase signaling in vitro and in vivo.

Published
2013
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47. Vascular endothelial growth factors and receptors : Anti-angiogenic therapy in the treatment of cancer

Author

Tugues, Sonia, Koch, Sina, Gualandi, Laura, Li, Xiujuan, Claesson-Welsh, Lena, Tugues, Sonia, Koch, Sina, Gualandi, Laura, Li, Xiujuan, and Claesson-Welsh, Lena

Abstract

Vascular endothelial growth factors (VEGFs) are critical regulators of vascular and lymphatic function during development, in health and in disease. There are five mammalian VEGF ligands and three VEGF receptor tyrosine kinases. In addition, several VEGF co-receptors that lack intrinsic catalytic activity, but that indirectly modulate the responsiveness to VEGF contribute to the final biological effect. This review describes the molecular features of VEGFs. VEGFRs and co-receptors with focus on their role in the treatment of cancer.

Published
2011
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48. Inhibition of Placental Growth Factor Activity Reduces the Severity of Fibrosis, Inflammation, and Portal Hypertension in Cirrhotic Mice

Author

Van Steenkiste, Christophe, Ribera, Jordi, Geerts, Anja, Pauta, Montse, Tugues, Sonia, Casteleyn, Christophe, Libbrecht, Louis, Olievier, Kim, Schroyen, Ben, Reynaert, Hendrik, van Grunsven, Leo A., Blomme, Bram, Coulon, Stephanie, Heindryckx, Femke, De Vos, Martine, Stassen, Jean Marie, Vinckier, Stefan, Altamirano, Jose, Bataller, Ramon, Carmeliet, Peter, Van Vlierberghe, Hans, Colle, Isabelle, Morales-Ruiz, Manuel, Van Steenkiste, Christophe, Ribera, Jordi, Geerts, Anja, Pauta, Montse, Tugues, Sonia, Casteleyn, Christophe, Libbrecht, Louis, Olievier, Kim, Schroyen, Ben, Reynaert, Hendrik, van Grunsven, Leo A., Blomme, Bram, Coulon, Stephanie, Heindryckx, Femke, De Vos, Martine, Stassen, Jean Marie, Vinckier, Stefan, Altamirano, Jose, Bataller, Ramon, Carmeliet, Peter, Van Vlierberghe, Hans, Colle, Isabelle, and Morales-Ruiz, Manuel

Abstract

Placental growth factor (PlGF) is associated selectively with pathological angiogenesis, and PlGF blockade does not affect the healthy vasculature. Anti-PlGF is therefore currently being clinically evaluated for the treatment of cancer patients. In cirrhosis, hepatic fibrogenesis is accompanied by extensive angiogenesis. In this paper, we evaluated the pathophysiological role of PlGF and the therapeutic potential of anti-PlGF in liver cirrhosis. PlGF was significantly up-regulated in the CCl4-induced rodent model of liver cirrhosis as well as in cirrhotic patients. Compared with wild-type animals, cirrhotic PlGF(-/-) mice showed a significant reduction in angiogenesis, arteriogenesis, inflammation, fibrosis, and portal hypertension. Importantly, pharmacological inhibition with anti-PlGF antibodies yielded similar results as genetic loss of PlGF. Notably, PlGF treatment of activated hepatic stellate cells induced sustained extracellular signal-regulated kinase 1/2 phosphorylation, as well as chemotaxis and proliferation, indicating a previously unrecognized profibrogenic role of PlGF. Conclusion: PlGF is a disease-candidate gene in liver cirrhosis, and inhibition of PlGF offers a therapeutic alternative with an attractive safety profile.

Published
2011
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49. Signal transduction by vascular endothelial growth factor receptors

Author

Koch, Sina, Tugues, Sonia, Li, Xiujuan, Gualandi, Laura, Claesson-Welsh, Lena, Koch, Sina, Tugues, Sonia, Li, Xiujuan, Gualandi, Laura, and Claesson-Welsh, Lena

Abstract

VEGFs (vascular endothelial growth factors) control vascular development during embryogenesis and the function of blood vessels and lymphatic vessels in the adult. There are five related mammalian ligands, which act through three receptor tyrosine kinases. Signalling is modulated through neuropilins, which act as VEGF co-receptors. Heparan sulfate and integrins are also important modulators of VEGF signalling. Therapeutic agents that interfere with VEGF signalling have been developed with the aim of decreasing angiogenesis in diseases that involve tissue growth and inflammation, such as cancer. The present review will outline the current understanding and consequent biology of VEGF receptor signalling.

Published
2011
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