Tumor-organism crosstalk

From a systemic perspective, tumors behave as organs which actively interact with the host (the patient). The last decades have shed light on the molecular and biological interactions between cancer cells with other cellular components inhabiting the tumor, the stroma. The latter includes different cells types such as cancer associated fibroblasts (CAF) and immune cells from both the lymphoid and myeloid lineages. The molecular mechanism behind these interactions are still in their infancy. More broadly, the tumor as a whole also establishes interactions with the vascular and the nervous system the nervous system that can affect the well-being of the patient. In this regard, anticancer strategies are currently focused on three main aspects of tumor-stroma interactions: the immune response to cancer, the metabolic rewiring of cancer and its impact on this cross-talk, and the interaction of the tumor with the microbiome.

    • Raúl V. Durán | Metabolism and cell signaling
    • Alicia G. Arroyo | Matrix metalloproteinases in angiogenesis and inflammation
    • José Antonio Pérez Simón | Cell therapy and new therapeutic targets in onco-hematology
    • Santos Mañes | Signaling networks in inflammation and cancer
    • Isabel Mérida | Diacylglycerol kinases in cancer immunity and immunotherapy
    • Timothy Thomson | Cancer metabolism and immunometabolism
    • Mar Valés Gómez | Tumor immune activation and evasion
    • Ana Cuenda | Stress protein kinases in cancer and inflammation
    • Jesús Pérez Losada | Molecular and genetic determinants of cancer susceptibility, evolution and treatment response
    • Lisardo Boscá | Cancer immunometabolism
    • Felipe X. Pimentel Muiños | Unconventional autophagy in health and disease
    • Esther Castellano Sánchez | Tumor stroma signaling
    • Sergio Casas-Tintó | Glia-neuron molecular signaling
    • María Domínguez | Mechanisms of growth control and cancer
    • Fernando Calvo | Tumour microenvironment
    • Fernando Martín Belmonte | Intestinal morphogenesis and homeostasis

METABOLISM AND CELL SIGNALING

RAÚL V. DURÁN – Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER)

Our research is focused on the crosstalk between cell signaling and metabolism in cancer. We investigate how cancer cells connect nutrient availability with mTOR pathway, a master regulator of cell growth. Our results indicated that this connection is a potential target for new therapeutic approaches against cancer.

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MATRIX METALLOPROTEASES IN ANGIOGENESIS AND INFLAMATION

ALICIA G. ARROYO – Centro de Investigaciones Biológicas Margarita Salas

Patrolling monocytes are innate immune cells responsible for inspecting the microvasculature through a crawling movement and capturing harmful particles in the bloodstream. Our group is elucidating the molecular actors involved in the uptake of circulating tumor cells by patrolling monocytes in order to reduce metastases, particularly in the lung.

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CELL THERAPY AND NEW THERAPEUTIC TARGETS IN ONCO-HEMATOLOGY

JOSÉ ANTONIO PÉREZ SÍMÓN – Instituto de Biomedicina de Sevilla

Traslational research in Hematology: Our main areas of interest are the following: 1. cell therapy and hematopoietic stem cell transplantation; 2. new therapeutic targets and 3. ex vivo and in animal models

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SIGNALING NETWORKS IN INFLAMMATION AND CANCER

SANTOS MAÑES – Centro Nacional de Biotecnología (CNB)

Immune evasion is a fundamental hallmark of cancer. We aim to identify, understand and manipulate tumor-induced resistance mechanisms with the hope to develop new immunotherapies against cancer. To this, our research focus on molecular circuits that regulate the inflammatory response to tumors, including the immune and the endothelial compartments.

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DIACYLGLYCEROL KINASES IN CANCER IMMUNITY AND IMMONOTHERAPY

ISABEL MÉRIDA – Centro Nacional Biotecnología (CNB)

Our group studies the contribution of Diacylglycerol Kinases (DGK) as negative regulators of T lymphocyte function against solid tumors. Our goal is to demonstrate that the inhibition of DGK activity represents a novel, understudied strategy in the management of a more effective immune response and/or treatment of cancer.

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CANCER METABOLISM AND IMMUNOMETABOLISM

TIMOTHY THOMSON – Instituto de Biología Molecular de Barcelona

Metabolic reprogramming and transactions in the tumor microenvironment. Combinatorial immunotherapy. The inflammasome.

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TUMOUR IMMUNE ACTIVATION AND EVASION

MAR VALÉS GÓMEZ – Centro Nacional de Biotecnología (CNB)

Our group is interested in cancer immunity mediated by Natural Killer (NK) cells and the molecular mechanisms of immune recognition and evasion. In particular, we study immunomodulatory molecules that are released in extracellular vesicles. We use ex vivo and in vitro models to understand human disease.

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STRESS PROTEIN KINASES IN CANCER AND INFLAMMATION

ANA CUENDA – Centro Nacional de Biotecnología (CNB)

Our group study the signaling pathways responsible for the relationship between inflammation and tumor development. We want to understand how the crosstalk between cancer, immune and stroma cells controls tumor initiation, progression and metastasis, as well as how they modulate the response to therapies. The final aim is the use this knowledge to improve existing therapies or to help in the designing of new ones.

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MOLECULAR AND GENETIC DETERMINANTS OF CANCER SUSCEPTIBILITY, EVOLUTION AND TREATMENT RESPONSE

JESÚS PÉREZ LOSADA – Instituto de Biología Molecular y Celular del Cáncer (IBMCC)

Cancer is a complex trait that results from other intermediate phenotypes involved in its development and evolution. The interactions between intermediate phenotypes generate a network of phenotypes located at different levels: systemic, organs, tissues, cells, and intracellular. We are interested in identifying genetic and molecular determinants at those different levels responsible for the different susceptibility and evolution of patients with the same type of cancer.

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CANCER IMMUNOMETABOLISM

LISARDO BOSCÁ – Instituto de Investigaciones Biomédicas “Alberto Sols”

We are interested in the study of the immune cells (myeloid and lymphoid) that are involved in the outcomes of drugs-treated cancer cells. We use human samples and myeloid and lymphoid human cells. Immunometabolic assays involve the use of 13C- and 15N- derived tracers to construct fluxomic maps.

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UNCONVENTIONAL AUTOPHAGY IN HEALTH AND DISEASE

FELIPE X. PIMENTEL MUIÑOS – Centro de Biología Molecular Severo Ochoa (CBMSO, CSIC-UAM)

We study the role of the autophagic machinery in the regulation of immunogenic cell death. We focus on the relative contribution of canonical and atypical mechanisms to this phenomenon with ultimate the intention of finding suitable therapeutic targets to improve the contribution of the immune system to cancer remission.

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TUMOR STROMA SIGNALING

ESTHER CASTELLANO SÁNCHEZ – Instituto de Biología Molecular y Celular del Cáncer (IBMCC)

Our main focus is to characterize the role of RAS signaling in tumour:stroma crosstalk to sustain lung tumour progression, with the aim of identifying new strategies to treat lung cancer patients

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GLIA-NEURON MOLECULAR SIGNALING

SERGIO CASAS-TINTÓ – Instituto Cajal

Glioblastoma (GB) is the most common and lethal type of cancer of the central nervous system, it is characterized by its aggressiveness, rapid cell proliferation and great infiltration capacity. GB cause progressive neurological dysfunction including memory loss, speech and language defects, epileptic seizures and vomits. There is no cure for this type of tumors and the median survival after optimal treatments (surgery, radiotherapy and chemotherapy) is 14,6 months. Our data indicate that GB cells develop a network of tumor microtubes (TMs) which confers resistance to the radiotherapy, contribute to the proliferation and dissemination of the tumor and provokes the degeneration of the neighboring neurons. Glial cells establish a network of projections to communicate and coordinate. Confocal image of a Drosophila third instar larvae brain. Glial cells and membranes are marked with myristoilatedRFP, neurons are marked with anti-HRP monoclonal antibody. We propose the study of signals that mediate GB and neuron communication and mediate GB progression and neurodegeneration. The mechanisms underlying these processes are proposed as a potential novel strategy against GB.

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MECHANISMS OF GROWTH CONTROL AND CANCER

MARÍA DOMÍNGUEZ – Instituto de Neurociencias

We leverage Drosophila cancer models to uncover the intricate pathways of cancer initiation and escape from innate antitumor immunity to more durable therapies. We also seek to identify resilience mechanisms that make some individuals, even carriers of cancer variants, remain free of the disease or fight it better than others.

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TUMOR MICROENVIRONMENT   

FERNANDO CALVO – Instituto de Biomedicina y Biotecnologia de Cantabria

Our research focuses on delineating the intricate crosstalk between cancer and stromal cells, and its impact on cancer initiation and progression. We are particularly interested in understanding the mechanisms controlling the pro-tumor behavior of cancer-associated fibroblasts (CAFs), and how they shape aggressive tumour microenvironments promoting cancer progression, dissemination and therapeutic resistance. The final goal is to harness that knowledge to inform novel diagnostic and therapeutic strategies for cancer patients.

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INTESTINAL MORPHOGENESIS AND HOMEOSTASIS    

FERNANDO MARTÍN BELMONTE – Centro de Biología Molecular Severo Ochoa & IRYCIS

Our main scientific interest is understanding the processes of intestinal cell communication, development and polarity during morphogenesis, homeostasis and regeneration, as well as their implications in human diseases, such as inflammatory bowel diseases (IBD), and cancer. Our research is based on the organ-on-a-chip epithelial cell cultures and the mouse intestine as model systems. We are focused on the analysis of genes that regulate epithelial polarity during morphogenesis, B cell response, and intestinal homeostasis, and particularly those that control signaling processes, membrane trafficking, and metabolic remodeling.

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