Tumour microenvironment and metabolism

Research works

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.

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.