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2. In vivo imaging of therapy-induced anti-cancer immune responses in humans

Author

Aarntzen, EHJG, Srinivas, M, Radu, CG, Punt, CJA, Boerman, OC, Figdor, CG, Oyen, WJG, and De Vries, IJM

Abstract

Immunotherapy aims to re-engage and revitalize the immune system in the fight against cancer. Research over the past decades has shown that the relationship between the immune system and human cancer is complex, highly dynamic, and variable between individuals. Considering the complexity, enormous effort and costs involved in optimizing immunotherapeutic approaches, clinically applicable tools to monitor therapy-induced immune responses in vivo are most warranted. However, the development of such tools is complicated by the fact that a developing immune response encompasses several body compartments, e.g., peripheral tissues, lymph nodes, lymphatic and vascular systems, as well as the tumor site itself. Moreover, the cells that comprise the immune system are not static but constantly circulate through the vascular and lymphatic system. Molecular imaging is considered the favorite candidate to fulfill this task. The progress in imaging technologies and modalities has provided a versatile toolbox to address these issues. This review focuses on the detection of therapy-induced anticancer immune responses in vivo and provides a comprehensive overview of clinically available imaging techniques as well as perspectives on future developments. In the discussion, we will focus on issues that specifically relate to imaging of the immune system and we will discuss the strengths and limitations of the current clinical imaging techniques. The last section provides future directions that we envision to be crucial for further development. © 2012 The Author(s).

Published
2013

4. Effective migration of antigen-pulsed dendritic cells to lymph nodes in melanoma patients is determined by their maturation state

Author

Vries, Ijm, Krooshoop, Djeb, Scharenborg, Nm, Lesterhuis, Wj, Diepstra, Jhs, Muijen, Gnp, Strijk, Sp, Ruers, Tj, Boerman, Oc, Wim J.G. Oyen, Adema, Gj, Punt, Cja, Figdor, Cg, and Other departments

Abstract

Dendritic cells are the professional antigen-presenting cells of the immune system. To induce an effective immune response, these cells should not only express high levels of MHC and costimulatory molecules but also migrate into the lymph nodes to interact with naïve T cells. Here, we demonstrate that in vitro-generated mature, but not immature dendritic cells, efficiently migrate into the T-cell areas of lymph nodes of melanoma patients. This difference is confirmed by in vitro studies, in which immature dendritic cells are strongly adherent, whereas mature dendritic cells remain highly motile. Our present findings demonstrate that the ability of dendritic cells to mount a proper immune response correlates with their ability to migrate both in vitro and in vivo

Published
2003

8. DC-ATLAS: a systems biology resource to dissect receptor specific signal transduction in dendritic cells

Author

Matthijs Kramer, Roberto Bonaiuti, Ivan Zanoni, Gerold Schuler, Walter Reith, Sorin Draghici, Damariz Rivero, Vassili Soumelis, Jonathan M. Austyn, Ugo D'Oro, Cornelis J. M. Melief, Andrea Splendiani, Carl G. Figdor, Maria Torcia, Enrica Calura, Marco Brandizi, Renato Ostuni, Sandra Gessani, Duccio Cavalieri, Francesca Granucci, Sonja I. Buschow, Maria Cristina Gauzzi, Arpad Lanyi, Stephan Schierer, Nadine van Montfoort, Éva Rajnavölgyi, Michaela Gündel, Philippe Pierre, Raphaël Zollinger, Luca Beltrame, Lisa Rizzetto, Andreas Baur, Isabelle Dunand-Sauthier, Carlotta De Filippo, Mirela Kuka, Evelina Gatti, Irene Stefanini, Razvan Popovici, Reith, Walter, Dunand-Sauthier, Isabelle, Pierre, Philippe, Università degli Studi di Firenze [Firenze], Radboud University Medical Center [Nijmegen], Istituto Superiore di Sanità, Rome (ISS), Department of Therapeutic Research and Medicines Evaluation, University of Geneva Medical School, Department of Pathology and Immunology, University of Erlangen, Department of Dermatology, Leaf Bioscience, Novartis Vaccines, Siena, Italy, Novartis Vaccines, Wayne State University [Detroit], Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), University of Milano-Bicocca (UNIMIB), Department of Biotechnology and Biosciences, University of Debrecen Egyetem [Debrecen], Leiden University Medical Center (LUMC), Miravtech Corporation, Immunité et cancer (U932), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie-Université Paris Descartes - Paris 5 (UPD5), University of Oxford [Oxford], Cavalieri, D, Rivero, D, Beltrame, L, Buschow, S, Calura, E, Rizzetto, L, Gessani, S, Gauzzi, M, Reith, W, Baur, A, Bonaiuti, R, Brandizi, M, De Filippo, C, D'Oro, U, Draghici, S, Dunand Sauthier, I, Gatti, E, Granucci, F, Gündel, M, Kramer, M, Kuka, M, Lanyi, A, Melief, C, Van Montfoort, N, Ostuni, R, Pierre, P, Popovici, R, Rajnavolgyi, E, Schierer, S, Schuler, G, Soumelis, V, Splendiani, A, Stefanini, I, Torcia, M, Zanoni, I, Zollinger, R, Figdor, C, Austyn, J, Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Dipartimento di Biotecnologie e Bioscienze = Department of Biotechnology and Biosciences [Milano-Bicocca] (BTBS), Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Buschow, Si, Gauzzi, Mc, Kuka, Mirela, Melief, Cj, van Montfoort, N, Torcia, Mg, Figdor, Cg, Austyn, J. M., Istituto Superiore di Sanità, Rome ( ISS ), Centre d'Immunologie de Marseille - Luminy ( CIML ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ), University of Milano-Bicocca ( UNIMIB ), Immunité et cancer ( U932 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Curie, Università degli Studi di Firenze = University of Florence (UniFI), Istituto Superiore di Sanità (ISS), Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Universiteit Leiden, and University of Oxford

Subjects
Cell type, Markup language, Computer science, Systems biology, medicine.medical_treatment, Immunology, Computational biology, ddc:616.07, computer.software_genre, 03 medical and health sciences, 0302 clinical medicine, Immune system, Immune Regulation [NCMLS 2], medicine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Elméleti orvostudományok, Molecular gastro-enterology and hepatology [IGMD 2], Molecular Biology, 030304 developmental biology, 0303 health sciences, Applied Mathematics, Research, Dendritic cells, toll like receptors, pattern recognition receptors, systems biology, Pattern recognition receptor, Immunotherapy, Orvostudományok, dendritic cells, toll-like receptors, TLR, TLR pathways, systems biology, pathway analysis, Computer Science Applications, Computational Theory and Mathematics, DECIPHER, [SDV.IMM]Life Sciences [q-bio]/Immunology, Data mining, Signal transduction, computer, 030215 immunology
Abstract

Contains fulltext : 88001.pdf (Publisher’s version ) (Closed access) BACKGROUND: The advent of Systems Biology has been accompanied by the blooming of pathway databases. Currently pathways are defined generically with respect to the organ or cell type where a reaction takes place. The cell type specificity of the reactions is the foundation of immunological research, and capturing this specificity is of paramount importance when using pathway-based analyses to decipher complex immunological datasets. Here, we present DC-ATLAS, a novel and versatile resource for the interpretation of high-throughput data generated perturbing the signaling network of dendritic cells (DCs). RESULTS: Pathways are annotated using a novel data model, the Biological Connection Markup Language (BCML), a SBGN-compliant data format developed to store the large amount of information collected. The application of DC-ATLAS to pathway-based analysis of the transcriptional program of DCs stimulated with agonists of the toll-like receptor family allows an integrated description of the flow of information from the cellular sensors to the functional outcome, capturing the temporal series of activation events by grouping sets of reactions that occur at different time points in well-defined functional modules. CONCLUSIONS: The initiative significantly improves our understanding of DC biology and regulatory networks. Developing a systems biology approach for immune system holds the promise of translating knowledge on the immune system into more successful immunotherapy strategies.

Published
2010

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