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Cell Plasticity within the Tumor Microenvironment January 8–12, 2017 | Big Sky, Montana | USA Scientific Organizers: Sergei Grivennikov, Fox Chase Cancer Center, USA Florian R. Greten, Institute for Tumor Biology and Experimental Therapy, Germany Mikala Egeblad, Cold Spring Harbor Laboratory, USA During the last decade, it has become unequivocally evident that tumor development is not a cell-autonomous process but rather depends on the intricate reciprocal interplay of mutant tumor cells with their local and distant environments. Composition and polarization of cells in the tumor microenvironment depends on genetic as well as environmental factors and is directly influenced by tumor therapy. Indeed, therapies that aim to shape the local immune milieu and consecutive signaling pathways in both stromal and tumor/stem cells address the complex pathophysiology of tumors more adequately and may therefore add substantial benefits for therapy. An absolute pre-requisite for such an endeavor is a comprehensive understanding of the exact molecular basis of the complex signaling networks in the tumor microenvironment that control the plasticity of both stromal and tumor cells, thereby shaping the complex cellular contexture, which ultimately forms a pro- or anti-tumorigenic milieu. Thus, this symposium aims to gather a comprehensive functional understanding of mediator-dependent cellular and molecular events that are responsible for the plasticity of both stromal and tumor/stem cells. It will bring together experts in cancer, stromal and immune cells to synthesize scientific knowledge about the phenomenon of cell plasticity within the tumor microenvironment, to define molecular and cellular pathways mediating plasticity and to propose approaches to interfere with cell plasticity for a new generation of effective therapeutic approaches in cancer and chronic injury. Importantly, it will bring together interdisciplinary groups of scientists or investigators who normally would not have an opportunity to meet (classical cancer biologists, tumor immunobiologists, stem cell experts and scientists working on stromal cells). Session Topics: • Plasticity of Epithelial, Cancer and Stem Cells • Plasticity and (Cancer) Stem Cell Niche • Cell Types Contributing to the Plasticity of Tumor Microenvironment • Plasticity of Immune Cells within the Tumor Microenvironment • Parallels between Normal Tissue Repair Response and Oncogenesis • Approaches to Visualize and Study Dynamics of Tumor Microenvironment (“Imaging”) • Targeting Changing Tumor Microenvironment for Anti-Cancer Therapies • Therapy Resistance Mediated by Adaptive Responses in Tumor Microenvironment plus two workshops Scholarship Application & Discounted Abstract Deadline: September 19, 2016 Abstract Deadline: October 6, 2016 Discounted Registration Deadline: November 8, 2016 Note: Scholarships are available for graduate students and postdoctoral fellows and are awarded based on the abstract submitted. Upper image of small breast tumor (blue) in its microenvironment, with blood vessels in green and macrophages in red, courtesy of Mikala Egeblad, Cold Spring Harbor Laboratory Meeting Hashtag: #KStme www.keystonesymposia.org/17A1 www.keystonesymposia.org/meetings | 1.800.253.0685 | 1.970.262.1230 a 501(c)(3) nonprofit educational organization KEYSTONE SYMPOSIA on Molecular and Cellular Biology Cell Plasticity within the Tumor Microenvironment (A1) January 8-12, 2017 • Big Sky Resort • Big Sky, Montana, USA Scientific Organizers: Sergei Grivennikov, Florian R. Greten and Mikala Egeblad Sponsored by Journal of Molecular Cell Biology (JMCB) and Roche Abstract & Scholarship Deadline: September 19, 2016 / Abstract Deadline: October 6, 2016 / Discounted Registration Deadline: November 8, 2016 SUNDAY, JANUARY 8 Arrival and Registration MONDAY, JANUARY 9 Welcome and Keynote Address *Sergei Grivennikov, Fox Chase Cancer Center, USA *Florian R. Greten, Institute for Tumor Biology and Experimental Therapy, Germany *Mikala Egeblad, Cold Spring Harbor Laboratory, USA Michael Karin, University of California, San Diego, USA Tumor-Elicited Inflammation and the Initiation of Colorectal Cancer Plasticity of Epithelial, Cancer and Stem Cells *Cédric Blanpain, Universite Libre de Bruxelles, Belgium *Shelly Peyton, University of Massachusetts, USA Florian R. Greten, Institute for Tumor Biology and Experimental Therapy, Germany Inflammatory Signaling in Intestinal Stem Cell Plasticity John Cassidy, University of Cambridge, UK Short Talk: The Development of Tamoxifen Resistance is Linked to Oct4 Driven Transcriptional Plasticity Andrew J. Ewald, Johns Hopkins University School of Medicine, USA Phenotypic Plasticity during Cell Invasion and Metastasis Kristiaan Lenos, Amsterdam Medical Center, Netherlands Short Talk: Spatiotemporal Regulation of Stem Cell Function in Colon Cancer Frederic J. de Sauvage, Genentech, Inc., USA Targeting Intestinal Stem Cells in Cancer Brian Bierie, Whitehead Institute for Biomedical Research, USA Poster Teaser: Integrin-Beta4 Identifies Cancer Stem Cell-Enriched Populations of Partially-Mesenchymal Carcinoma Cells Jessica L. Christenson, University of Colorado, USA Poster Teaser: The Role of the Androgen Receptor in Triple-Negative Breast Cancer Progression: Tumor-Intrinsic and Tumor-Extrinsic Mechanisms Ryan Carpenter, University of Massachusetts, Amherst, USA Poster Teaser: Capturing Microenvironmental Regulation of Metastatic Dormancy and Recurrence Sara E. Berkey, University of Pittsburgh, USA Poster Teaser: The IL17+Foxp3+ and exTh17 Foxp3+ Plastic T Cells Comprise Novel Immunosuppressive Regulatory T Cell Subsets in Tumors Oxana Dmitrieva, Fox Chase Cancer Center, USA Poster Teaser: The Role of IL-1R-Signaling in Tumor Elicited Inflammation and Colon Cancer Workshop 1: Plasticity and the Cancer Stem Cell Niche *Diana Leigh Avery, University of Pennsylvania School of Medicine, USA Matrix Mechanics and Composition Dictate Stromal Cell Differentiation in Lung Tumorigenesis Ikbale El Ayachi, University of Tennessee Health Science Center, USA The Absence of Wnt10b Expression Inhibits Tumor Initiation and Metastasis Modulating Stroma-Tumor Microenvironment Homeostasis *Loukia Georgiou Karacosta, Stanford University, USA Identifying Dynamic EMT Transition States in Lung Cancer Using Single Cell Multidimensional Analysis Hazel Quinn, Max Delbruck Centre, Germany Genetically Interfering with the Tumor Microenvironment via Shh in Wnt-Met driven Mouse Triple Negative Breast Cancer Michael Buchert, Olivia Newton-John Cancer Research Institute, Australia Insights into the Role of DCLK1 as a Novel Driver of Gastric Cancer Toni Celia-Terrassa, Princeton University, USA Pathways Regulating the Evasion of Normal and Cancer Stem Cells from Interferon-Imposed Constraint Dejan Maglic, Boston Children's Hospital, USA The Hedgehog and Hippo Pathways Cooperate in BCC Initiation and Progression Hélène Salmon, Icahn School of Medicine at Mount Sinai, USA The Tumor Microenvironment Controls Tumor Response to Checkpoint Blockade Plasticity and the (Cancer) Stem Cell Niche *Florian R. Greten, Institute for Tumor Biology and Experimental Therapy, Germany *Louis Vermeulen, CEMM, Netherlands Jing Yang, University of California, San Diego, USA Epithelial-Mesenchymal Plasticity in Carcinoma Metastasis Cédric Blanpain, Universite Libre de Bruxelles, Belgium Skin Tumor Stemness and Progression Ekrem Emrah Er, Memorial Sloan Kettering Cancer Center, USA Short Talk: Pericytic Spreading of Disseminated Cancer Cells Initiate Multi-Organ Metastasis Mathias Florian Heikenwälder, German Cancer Research Center, DKFZ, Germany Kupffer-Cell Derived TNF Preferentially Triggers Cholangiocellular Carcinoma through JNK under Chronic Mitochondrial Dysfunction and ROS Poster Session 1 TUESDAY, JANUARY 10 Cell Types Contributing to the Plasticity of the Tumor Microenvironment *Jing Yang, University of California, San Diego, USA *Sandra S. McAllister, Brigham & Women's Hospital/Harvard Medical School, USA Thomas Tüting, Otto-von-Guericke University, Germany Inflammation-Induced Phenotypic Plasticity of Tumor and Immune Cells as a Mechanism of Disease Progression and Therapy Resistance in Melanoma Neta Erez, Tel Aviv University, Israel Short Talk: Cancer-Associated Fibroblasts Link Tissue Damage with Tumor-Promoting Inflammation in Breast Cancer * Session Chair † Invited but not yet accepted Program current as of May 6, 2017. Program subject to change. Meal formats are based on meeting venue. For the most up-to-date details, visit www.keystonesymposia.org/17A1. KEYSTONE SYMPOSIA on Molecular and Cellular Biology Cell Plasticity within the Tumor Microenvironment (A1) January 8-12, 2017 • Big Sky Resort • Big Sky, Montana, USA Scientific Organizers: Sergei Grivennikov, Florian R. Greten and Mikala Egeblad Sponsored by Journal of Molecular Cell Biology (JMCB) and Roche Abstract & Scholarship Deadline: September 19, 2016 / Abstract Deadline: October 6, 2016 / Discounted Registration Deadline: November 8, 2016 Brian W. Wong, Vesalius Research Center, Belgium Endothelial versus Cancer Cell Metabolism Valerie M. Weaver, University of California, San Francisco, USA Extracellular Matrix and Tumor Mechanics Shelly Peyton, University of Massachusetts, USA Short Talk: Dynamics of Fibronectin Assembly and Tumor Cell Latency Raghu Kalluri, University of Texas MD Anderson Cancer Center, USA The Functional Role of EMT and Exosomes in Pancreatic Cancer Chen Hao Lo, Moffitt Cancer Center, USA Poster Teaser: Temporal Dynamics of Macrophage Plasticity in Bone Metastatic Prostate Cancer Magdolna Djurec, Spanish National Cancer Research Center, Spain Poster Teaser: Reprogramming Cancer Associated Fibroblasts as a Therapeutic Approach against Pancreatic Ductal Adenocarcinoma Ayse Nihan Kilinc, University of Basel, Switzerland Poster Teaser: The Contribution of Epithelial-Mesenchymal Plasticity to Cancer Stemness Lennart Kester, Hubrecht Institute, Netherlands Poster Teaser: Clonal Dynamics with Single Cell Resolution in Different Stages of Colon Carcinoma Natsuko Kimura, University of Tokyo, Japan Poster Teaser: Maintenance of Stemness and Niche Environment of Breast Cancer Cells by FRS2beta, a Feedback Inhibitor for HER2-ERK Pathway, during Mammary Tumorigenesis Plasticity of Immune Cells within the Tumor Microenvironment *Mikala Egeblad, Cold Spring Harbor Laboratory, USA *Alana L. Welm, Huntsman Cancer Institute, University of Utah School of Medicine, USA Peter Friedl, NCMLS, Radboud University Nijmegen Medical Centre, Netherlands Serial Killing of Tumor Cells – Impact of the Microenvironment Giorgio Trinchieri, NCI, National Institutes of Health, USA Cancer as a Meta-Organism – Fine-Tuning of Tumor Progression and Response to Therapy by Microbiota-Regulated Immune Cells Melissa A. Meyer, Washington University in St. Louis, USA Short Talk: Tumor-Induced IRF8 Deficiency Interrupts BATF3-Dependent Dendritic Cells Development Sergei Grivennikov, Fox Chase Cancer Center, USA Tumor-Elicited Inflammation and Cytokines at Crossroads in Wound Healing and Tumor Progression Poster Session 2 WEDNESDAY, JANUARY 11 Parallels between Normal Tissue Repair Response and Oncogenesis *Carla V. Rothlin, Yale University, USA *Neta Erez, Tel Aviv University, Israel Erik A. Sahai, Cancer Research UK London Research Institute, UK Tumor-Stroma Cross-Talk in Metastasis and Therapy Failure Andreas Trumpp, German Cancer Research Center, Germany Stratification and Resistance Mechanisms in Pancreatic Cancer Annelise Snyder, University of Washington, USA Short Talk: Necroptotic Cell Death within the Tumor Microenvironment Promotes Tumor Control Alana L. Welm, Huntsman Cancer Institute, University of Utah School of Medicine, USA Ron Kinase in Bone Remodeling and Bone Metastasis Sheila A. Stewart, Washington University School of Medicine, USA Short Talk: Inhibition of Stromal p38MAPK Abrogates Breast Cancer Metastases Robert F. Schwabe, Columbia University, USA Fibrosis Promotes the Development of Liver Cancer Mario A. Shields, Cold Spring Harbor Laboratory, USA Poster Teaser: Lysyl Oxidases Suppress Pancreatic Cancer Progression and Inhibit FAK and ERK Signaling Suzanne M. Ponik, University of Wisconsin-Madison, USA Poster Teaser: Collagen Matrix Density Drives the Metabolic Profile Shift of Breast Cancer Cells Daniel C. Rabe, University of Chicago, USA Poster Teaser: Exosome Crosstalk between Tumors and Tumor-Associated Macrophages Drives Pro-Invasive Plasticity Julia Varga, Georg Speyer Haus, Germany Poster Teaser: Notch3 Activation in Response to Aberrant Akt Signaling Contributes to Colorectal Cancer Progression Workshop 2: Therapy Resistance Mediated by Adaptive Responses in the Tumor Microenvironment *Weizhou Zhang, University of Iowa, USA Saran Kumar, Hebrew University, Israel Adjacency to Blood Vessels as a Generator of Tumor Cell Metabolic and Phenotypic Heterogeneities Mihaela Skobe, Icahn School of Medicine at Mount Sinai, USA Lymphatic Endothelium Protects Breast Cancer Cells from Death by Inducing Metabolic Adaptations Melissa R. Junttila, Genentech, Inc., USA Identification of a Non-Genomic Resistance Mechanism to Vemurafenib in a BRAF Mutant Melanoma Model Peter Chockley, University of Michigan Medical School, USA EMT Confers Susceptibility to Metastasis-Specific Immune Surveillance in Lung Cancer Alex Swarbrick, Garvan Institute of Medical Research, Australia The Paracrine Hedgehog-FGF Axis Mediates Cancer Stem Cell Plasticity in Triple Negative Breast Cancer *Ela Elyada, Cold Spring Harbor Laboratory, USA Pancreatic Stellate Cell Dynamics in PDAC Michael Timaner, Technion-Israel Institute of Technology, Israel Tumor-Associated Mesenchymal Stem Cells Preserve Cancer Stem Cells Niche in the Tumor Microenvironment Following Chemotherapy * Session Chair † Invited but not yet accepted Program current as of May 6, 2017. Program subject to change. Meal formats are based on meeting venue. For the most up-to-date details, visit www.keystonesymposia.org/17A1. KEYSTONE SYMPOSIA on Molecular and Cellular Biology Cell Plasticity within the Tumor Microenvironment (A1) January 8-12, 2017 • Big Sky Resort • Big Sky, Montana, USA Scientific Organizers: Sergei Grivennikov, Florian R. Greten and Mikala Egeblad Sponsored by Journal of Molecular Cell Biology (JMCB) and Roche Abstract & Scholarship Deadline: September 19, 2016 / Abstract Deadline: October 6, 2016 / Discounted Registration Deadline: November 8, 2016 Approaches to Visualize and Study Dynamics of the Tumor Microenvironment (“Imaging”) *Sergei Grivennikov, Fox Chase Cancer Center, USA *Stefani Spranger, University of Chicago, USA Mikala Egeblad, Cold Spring Harbor Laboratory, USA Imaging Reveals Tumor and Stromal Contributions to Formation of Metastases Danielle Seinstra, Hubrecht Institute, Netherlands Plasticity Between Epithelial and Mesenchymal States Unlinks EMT from Metastasis-Enhancing Stem Cell Capacity Tracy W. Liu, MD Anderson Cancer Center, USA Short Talk: Imaging the Dynamics of Tumor NF-kB Transcriptional Activation and the Microenvironment In Vivo Matthew F. Krummel, University of California, San Francisco, USA Imaging and Deconvolving Tumor Antigen Flow in Primary and Metastatic Tumor Sites *Sergei Grivennikov, Fox Chase Cancer Center, USA *Florian R. Greten, Institute for Tumor Biology and Experimental Therapy, Germany *Mikala Egeblad, Cold Spring Harbor Laboratory, USA Robert A. Weinberg, Massachusetts Institute of Technology, USA The Epithelial-Mesenchymal Transition and Malignant Progression Meeting Wrap-Up: Outcomes and Future Directions (Organizers) FRIDAY, JANUARY 13 Departure Poster Session 3 THURSDAY, JANUARY 12 Targeting the Changing Tumor Microenvironment for Anti-Cancer Therapies *Sheila A. Stewart, Washington University School of Medicine, USA *Andrew J. Ewald, Johns Hopkins University School of Medicine, USA Karin E. de Visser, Netherlands Cancer Institute, Netherlands EMBO Young Investigator Lecture: Targeting Tumor-Induced Systemic Inflammation to Fight Metastatic Breast Cancer Carla V. Rothlin, Yale University, USA Innate Immune Checkpoints in Anti-Tumor Immunity Deepak Nagrath, University of Michigan, USA Short Talk: Targeting Glutamine Synthetase in Tumors Disrupts Tumor Microenvironment-Regulated Cancer Cell Growth Sandra S. McAllister, Brigham & Women's Hospital/Harvard Medical School, USA Systemic Regulation of Tumor and Stromal Cell Plasticity Lionel J. Apetoh, Centre Georges Francois Leclerc, France Short Talk: Selective Degradation of the PU.1 Transcription Factor by Autophagy Represses TH9 Cell Differentiation Paula D. Bos, Virginia Commonwealth University, USA Short Talk: Treg-ulation of the Breast Tumor Microenvironment Weizhou Zhang, University of Iowa, USA Short Talk: Obesity-Related NLRC4 Inflammasome Activation and Angiogenesis in Breast Cancer Therapy Resistance Mediated by Adaptive Responses in the Tumor Microenvironment *Karin E. de Visser, Netherlands Cancer Institute, Netherlands *Erik A. Sahai, Cancer Research UK London Research Institute, UK Francois Ghiringhelli, Centre de Recherche, INSERM U866, France Chemotherapy and Reprogramming Immune and Cancer Cells Stefani Spranger, University of Chicago, USA Impact of Tumor Cell-Intrinsic Signaling on Anti-Tumor Immune Responses in the Tumor Microenvironment Closing Keynote Address * Session Chair † Invited but not yet accepted Program current as of May 6, 2017. Program subject to change. Meal formats are based on meeting venue. For the most up-to-date details, visit www.keystonesymposia.org/17A1.