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ProDoc Cell Migration Research Module 3: Soluble factors in Cell Migration

English title ProDoc Cell Migration Research Module 3: Soluble factors in Cell Migration
Applicant Bourquin Carole
Number 141773
Funding scheme ProDoc
Research institution Département de Médecine Université de Fribourg
Institution of higher education University of Fribourg - FR
Main discipline Immunology, Immunopathology
Start/End 01.10.2012 - 31.10.2016
Approved amount 691'150.00
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All Disciplines (2)

Discipline
Immunology, Immunopathology
Experimental Cancer Research

Keywords (4)

Cell migration; immune cell trafficking; metastasis; chemokines

Lay Summary (French)

Lead
Lay summary

La migration de cellules du corps humain, c’est à dire leur déplacement contrôlé à l’intérieur de l’organisme, par exemple vers un site d’inflammation, est essentielle pour une défense immunitaire efficace. Cependant, la migration cellulaire joue également un rôle important pour la dissémination du cancer sous forme de métastases. Le contrôle de cette migration se fait par l’intermédiaire de molécules endogènes, les chimiokines, qui attirent les cellules migrantes hors des vaisseaux sanguins et les positionnent dans les tissus. Ces chimiokines, qui se lient à des récepteurs à la surface des cellules migrantes, jouent un rôle à la fois pour la migration des cellules immunitaires et pour la dissémination des cellules cancéreuses. Dans ce module de recherche associant des chercheurs de l’Université de Fribourg, de l’Université de Berne et de l’Institut de Recherche en Biomédecine de Bellinzona, nous allons étudier les chimiokines ainsi que leurs récepteurs qui contrôlent la migration cellulaire lors de pathologies inflammatoires ou cancéreuses.

Dans un premier projet, nous étudierons le rôle des récepteurs de chimiokines CCR2 et CXCR1 pour la migration de cellules immunitaires leucocytaires dans le cerveau lors de pathologies inflammatoires telles que la sclérose en plaques. Nous utiliserons des modèles récemment développés dans le laboratoire et des techniques d’imagerie de pointe.

Dans un deuxième projet, nous étudierons comment les synergies entre différentes chimiokines modulent la migration de cellules immunitaires vers les tumeurs. Les résultats de ce projet permettront de mieux comprendre comment se développe une réponse immunitaire contre le cancer et comment la soutenir par des moyens pharmacologiques. Dans un troisième projet, nous évaluerons comment les chimiokines influencent le développement de métastases dans le cancer du sein.

Ces recherches seront faites en étroite collaboration avec les institutions partenaires et permettront des avances qui seraient plus difficiles pour des laboratoires individuels. Les résultats de ces travaux permettront de mieux comprendre les mécanismes qui guident la migration de cellules immunitaires et tumorales. Ces nouvelles connaissances seront directement applicables au développement de nouvelles thérapies dans le domaine des maladies inflammatoires et du cancer.

Pour plus d’informations: www.cell-mig.ch


Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Amphiphilic nanoparticle delivery enhances the anticancer efficacy of a TLR7 ligand via local immune activation
Mottas Inès, Bekdemir Ahmet, Cereghetti Alessandra, Spagnuolo Lorenzo, Yang Yu-Sang Sabrina, Müller Marie, Irvine Darrell J., Stellacci Francesco, Bourquin Carole (2019), Amphiphilic nanoparticle delivery enhances the anticancer efficacy of a TLR7 ligand via local immune activation, in Biomaterials, 190-191, 111-120.
NAB2 is a novel immune stimulator of MDA-5 that promotes a strong type I interferon response
Oberson Anne, Spagnuolo Lorenzo, Puddinu Viola, Barchet Winfried, Rittner Karola, Bourquin Carole (2018), NAB2 is a novel immune stimulator of MDA-5 that promotes a strong type I interferon response, in Oncotarget, 9(5), 5641-5651.
Arginase inhibition suppresses lung metastasis in the 4T1 breast cancer model independently of the immunomodulatory and anti-metastatic effects of VEGFR-2 blockade
Secondini Chiara, Coquoz Oriana, Spagnuolo Lorenzo, Spinetti Thibaud, Peyvandi Sanam, Ciarloni Laura, Botta Francesca, Bourquin Carole, Rüegg Curzio (2017), Arginase inhibition suppresses lung metastasis in the 4T1 breast cancer model independently of the immunomodulatory and anti-metastatic effects of VEGFR-2 blockade, in OncoImmunology, 6(6), e1316437-e1316437.
Reprogramming of TLR7 signaling enhances anti- tumor NK and cytotoxic T cell responses.
Hotz C Treinies M Mottas I Rötzer L Oberson A Perdicchio M Spagnuolo L Spinetti T Herbst T (2016), Reprogramming of TLR7 signaling enhances anti- tumor NK and cytotoxic T cell responses., in Oncoimmunology, 5(11), e1232219.
Chemokine interaction with synergy‐inducing molecules: fine tuning modulation of cell trafficking
Cecchinato Valentina, D'Agostino Gianluca, Raeli Lorenzo, Uguccioni Mariagrazia (2015), Chemokine interaction with synergy‐inducing molecules: fine tuning modulation of cell trafficking, in Journal of Leukocyte Biology, 99(6), 851-855.
Fine tuning modulation of chemokine activities induced by synergy-inducing molecules.
Cecchinato Valentina, D'Agostino Gianluca, Raeli Lorenzo, Uguccioni Mariagrazia, Fine tuning modulation of chemokine activities induced by synergy-inducing molecules., in Journal of Leukocyte Biology.
TLR7-based cancer immunotherapy decreases intratumoral myeloid-derived suppressor cells and blocks their immunosuppressive function.
Spinetti T Spagnuolo L Mottas I Secondini C Treinies M Rüegg C, TLR7-based cancer immunotherapy decreases intratumoral myeloid-derived suppressor cells and blocks their immunosuppressive function., in Oncoimmunology, 5(11), e1230578.

Collaboration

Group / person Country
Types of collaboration
BayImmuNet Immunotherapy Network Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Prof. Roland Martin, Neurologische Klinik, Universitätsspital Zürich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Prof. Eric Alléman, University of Geneva Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Prof. Marco Bianchi Italy (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Prof. Elisabetta Dejana, Milan Italy (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Research Training Group 1202, German Research Foundation Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Industry/business/other use-inspired collaboration
FP7 JUSTBRAIN Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof. Dan Bullard, Birmingham United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
FP7 European Stroke Network Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Exchange of personnel
Prof. Richard Ransohoff, Cleveland United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof. Joshua Weiner, Iowa United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Spring Meeting of the Swiss Society of Pharmacology and Toxicology Talk given at a conference “Downregulation of intratumoral HMGB1 reduces tumor growth by an immune-mediated mechanism” 19.04.2018 Berne, Switzerland Spagnuolo Lorenzo; Bourquin Carole;
Forum graduate schools infection and Immunity Talk given at a conference “Mixed-lingand coated gold nanoparticles to improve efficacy of immuno-stimulating drugs" 12.05.2017 Geneva, Switzerland Bourquin Carole; Spagnuolo Lorenzo;
14th CIMT Annual Meeting, Mainz, Germany, 10th-12th May, 2016 Poster HMGB1 impacts B-cell migration 10.05.2016 Mainz, Germany Bourquin Carole; Spagnuolo Lorenzo;
. 10th World Immune Regulation Meeting, Davos, 16th-19th March, 2016 Talk given at a conference HMGB1 impacts B-cell migration 16.03.2016 Davos, Switzerland Spagnuolo Lorenzo;
European Congress of Immunology Poster Poster 06.09.2015 Wien, Austria D'Agostino Gianluca;
First European Chemokine and Cell Migration Conference Poster poster 04.06.2015 Villars-sur-Ollon, Switzerland D'Agostino Gianluca;
IX World Immune Regulation Meeting Talk given at a conference workshop oral presenation, poster presentation 18.03.2015 Davos, Switzerland Spagnuolo Lorenzo;
11th Spring School of Immunology of DGfI Poster poster 08.03.2015 Ettal, Germany Spagnuolo Lorenzo;
Midwinter Conference Advances in Immunology Poster poster 17.01.2015 Seefeld, Austria Spagnuolo Lorenzo;
International Summerschool Bern Immunology Club, Stein am Rhein 27. to 29. July, 2014 Talk given at a conference Oral presentation 27.07.2014 Stein am Rhein, Switzerland Habbita Naïma;
3rd Research Day in Medicine, University of Fribourg Poster Poster 21.05.2014 Fribourg, Switzerland Spagnuolo Lorenzo;
XXV Meeting of the Swiss Immunology PhD students, Wolfsberg Poster Poster 03.04.2013 Wolfsberg, Switzerland Spagnuolo Lorenzo;


Communication with the public

Communication Title Media Place Year
Other activities Children's workshop "Découvrez un médicament" German-speaking Switzerland Western Switzerland 2014
Talks/events/exhibitions Das Virus und das verlorene Schuh German-speaking Switzerland 2014

Awards

Title Year
Young scientist travel award, CIMT meeting in Mainz, Germany, 10th-12th May, 2016 2016

Associated projects

Number Title Start Funding scheme
149420 Identification of trafficking molecules involved in the migration of CD8 T cells across the blood-brain barrier during immunosurveillance and neuroinflammation 01.10.2013 Project funding (Div. I-III)
137087 Cell Migration 01.09.2011 ProDoc
137079 Cell migration in tumorigenesis and metastasis 01.01.2012 ProDoc
156372 RLR/TLR combination therapy: Mechanisms of T-cell recruitment into gastric tumors 01.06.2015 Project funding (Div. I-III)
157752 Microchip-based flow cell sorting in biomedicine and material sciences 01.05.2015 R'EQUIP
182317 HMGB1 and Gasdermin D: intratumoral targets to improve the response to cancer immunotherapy 01.01.2019 Project funding (Div. I-III)
137127 ProDoc Cell Migration Research Module I: Immune cell migration in immunosurveillance and inflammation 01.10.2011 ProDoc
137087 Cell Migration 01.09.2011 ProDoc

Abstract

Cell migration is fundamental to immunosurveillance and inflammation but also to tumor invasion and metastatic dissemination. Chemokines and their receptors play a central role in positioning immune and tumor cells with spatiotemporal precision. In the multi-step extravasation of circulating cells, chemokines trigger their arrest to the vascular endothelium, then make them move across the vascular wall and along surface-bound chemokine gradients to their destination. In the immune system, this is relevant to homeostatic recirculation of lymphocytes through lymphatic tissues as well as to recruitment of leukocytes to tissues during acute or chronic inflammation. In cancer, in addition to migration, chemokines also promote tumor cell proliferation and survival, and contribute to the formation of metastatic niches. Thus expression of chemokine receptors on circulating immune or tumor cells is critical to coordinate complex tissue responses. In addition to chemokines a number of factors (e.g. HGF or Ang2) have been recognized to exert chemotactic activity. In this ProDoc Research Module (RM) three PhD students will work on complementary and interlaced projects dedicated to address the roles of chemotactic factors and their cognate receptors in myeloid, lymphoid and tumor cell migration. The knowledge obtained will be integrated into our current understanding of the cellular and molecular basis of pathophysiological events such as acute and chronic inflammation, tumor progression and metastasis. Results generated by this research module have the potential to guide the development of novel therapeutic strategies. The present RM will be integrated as RM3 in a highly synergistic manner (as outlined in the cartoon below) in the existing ProDoc CellMigration, which currently consists of a Training Module (TM), and two research modules, RM1 and RM2. Associating RM1 with RM3, ProDoc Student 13 will investigate the role of CCR2, CX3CR1, Tie2 and their respective ligands in the migration of myeloid subsets into the brain during immunosurveillance and neuroinflammatory disorders such as multiple sclerosis. To this purpose this student will use novel mouse models and mesoscopic and live cell imaging tools and human samples. Research of ProDoc Student 14 will define how synergies between soluble mediators enhance T cell recruitment into tumors, with relevance to natural anti-tumor immune responses and cancer immunotherapy protocols. Work by this student with have natural interactions with RM1 and RM2. Finally, ProDoc Student 15 will study the modulation of chemokine activity in spontaneous and therapy-induced breast cancer metastasis by exploiting recent results and tumor models obtained in the partner laboratories. Research topics addressed within RM3 will be highly related and complementary to experiments proposed in RM1 and RM2 of the running ProDoc CellMigration Program. Embedding three additional PhD students to work in collaborative projects focusing on the role of soluble mediators involved in immune and tumor cell migration will exploit to the fullest the potential for collaborative efforts within the ProDoc consortium. This program provides the framework for an internationally visible training program for highly qualified PhD students in the field of cell migration, excellence of which cannot be achieved at this level in the individual laboratories alone.
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