Tumour microenvironment and metabolism
It is now accepted that tumours are heterogeneous in their composition, including, in addition to tumour cells, stromal cells and the extracellular matrix, which can make up to 90% of the mass of solid tumours. The tumour microenvironment has only been considered in the study of the biology of solid tumours and their response to therapy in the last 15 years, but it is now a major field of research. However, the critical role of the “niche” has been known for some 30 years in haematopoietic stem cells, and the ever new knowledge that has emerged from it represents a wealth of information. The concepts of local and distant niches involving respectively, juxtacrine and paracrine dialogues between tumour and stromal cells within the primary tumour, or endocrine within “pre-metastatic” sites, have increased our understanding of the tumour biology at the scale of the whole organism.
Within the CRCT, some fifteen projects are being developed in nine teams belonging to the “Tumour microenvironment and metabolism” axis. Their aim is to identify targets in both tumour cells and the stroma, the co-targeting of which would enable to sensitize tumours to therapies and/or to abrogate their metastatic potential. To do this, the biology of all these cells must be studied in complex in vitro and in vivo models in which direct and indirect cellular and acellular communications faithfully reproduce the human pathology. The strong partnership of the CRCT teams with the clinical services of the Toulouse University Cancer Institute is essential in the setting up of models derived from patient tissue samples. The accessibility of the CREFRE’s zootechnical platforms allows the setting up of spontaneous or grafted cancer models, which represent the best preclinical tools for testing new therapeutic combinations, before their transfer to a clinical trial in patients. The CRCT teams are developing models of cancers that are particularly aggressive due to their resistance to therapies (acute and chronic leukaemia, lymphoma, glioblastoma, breast and lung cancers, melanoma, and ovarian and pancreatic cancers).
The work and expertise of the teams is focused on the biology of mesenchymal stromal cells, cancer-associated fibroblasts, adipocytes, endothelial cells or normal epithelial cells. The aim is to explore how these cells interact with each other and with tumour cells, directly or indirectly, respectively through the secretion of extracellular matrices and vesicles, or diffusible factors (e.g. metabolites), to functionally impact tumour aggressiveness (genetic, epigenetic, metabolic reprogramming, cell self-renewal, metastasis, resistance to treatments) or immune cell function (recruitment, polarisation and activation within the tumour). Understanding the biology of these dialogues, how they are generated in each cell subtype (signalling, metabolism), and modulated by external environmental factors (oxygen and nutrient deprivation) or by therapies targeting tumour cells (targeted therapies or chemotherapies), is critical to enable the design of new synergistic therapeutic strategies targeting both tumour and stromal compartments. The complementarity and interactions of the CRCT teams has enabled to fund inter-CRCT team projects (Cancéropole GSO, Toulouse Cancer Santé Foundation, INCa) and to publish some thirty joint-publications since the creation of the axis (see list). To do this, the teams rely on the accessibility of the platforms and expertise of the CRCT’s technology centre, as well as the other GenoTOUL technology platforms in Toulouse, including MetaToul for the analysis of metabolic tumour reprogramming, a key theme of the site.
This axis is coordinated by Corinne Bousquet.
involved in this axis
Bruno Segui, Nathalie Andrieu + 21 collaborators
Ceramide metabolism in melanoma: from basic mechanisms to immunotherapy
Corinne Bousquet + 18 collaborators
MICROPANC : Microenvironnement and Therapeutic Resistance in Pancreatic Neoplasms
Camille Laurent + 21 collaborators
New Immunotherapies Against Lymphoma
Pierre Cordelier + 21 collaborators
ImPact : Innovation in pancreatic cancer therapy
Elizabeth Cohen-Jonathan Moyal + 22 collaborators
RADOPT : Optimisation de la radiothérapie: des voies de signalisation moléculaires aux essais cliniques
Marc Poirot, Sandrine Silvente-Poirot + 15 collaborators
Cholesterol Metabolism and Therapeutic Innovations
Julie Guillermet-Guibert + 11 collaborators
SigDYN : Integrated cellular signalling and PI3K isoforms
Jean-Emmanuel Sarry + 31 collaborators
METAMAL : Metabolism and Therapeutic Resistance In Acute Myeloid Leukemia
Véra Pancaldi + 10 collaborators
NetB(IO)² : Network Biology for Immuno-oncology
Centre de Recherches en Cancérologie de Toulouse (Oncopole)
Toulouse – FR
05 82 74 15 75
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