Thematic Axis: Microenvironment and Tumoral heterogeneity

Head of the axis : Céline Delloye-Bourgeois

A key area of research at the CRCL focuses on the tumor microenvironment and its intricate relationships with tumor heterogeneity—two factors that have a major impact on tumor development and response to treatment. The tumor microenvironment refers to the complex network of secreted molecules, cell types, blood vessels and nerves that surround and are part of the tumor. These various components engage in bidirectional communication with tumor cells, which modulates the properties of the entire tumor ecosystem. Specifically, tumor heterogeneity, which describes the diversity of cancer cells within a tumor tissue, is closely linked to the tumor microenvironment. It arises from a range of factors, including the cell or tissue of origin, genetic mutations, epigenetic changes, and the diverse influences of the microenvironment on cancer cells. The complexity and diversity of both the tumor microenvironment and cancer cells within a tumor—and between patients—make the design of efficient and specific treatments highly challenging.
By dissecting the structural and functional properties of the tumor microenvironment and their link with cancer heterogeneity, our research teams aim to uncover novel mechanisms of tumor progression and resistance ultimately paving the way for more effective and personalized therapies for cancer patients.

Microenvironmental signalling in tumour dissemination

Team leader: Julien Ablain
The ABLAIN team investigates the molecular mechanisms by which melanoma cells sense various local signals within the primary tumor and that regulate their spreading behavior.

Apoptosis, cancer and development

Team leader: Patrick Mehlen
The MEHLEN team has developed therapeutic strategies blocking netrin-1 in tumors with clinical activity associated with major changes in the immune infiltrate. This team is thus actively pursuing the crosstalk between cancer cells and stromal cells including both cancer-associated fibroblasts, endothelial cell and immune cells.

BMP, Ecosystem, stemness and dynamic in cancer

Team leaders: Véronique Maguer-satta
The MAGUER-SATTA team aims to identify key elements of adaptation and remodeling of the microenvironment in bone marrow metastasis and leukemia relapse.

Cancer cell death

Team leader: Gabriel Ichim
The ICHIM team investigates how cancer cells interact with the process of cell death, both intrinsically and extrinsically. They’re especially interested in understanding how cell death itself—and its main players—might actually boost oncogenesis.

Cancer cell plasticity in melanoma

Team leaders: Julie Caramel et Stéphane Dalle
The CARAMEL/DALLE team characterizes the role of the crosstalk between melanoma cell states heterogeneity and the tumor microenvironment in promoting melanoma progression and resistance to treatment (in both mouse models and human samples).

Cell States and Childhood Cancers

Team leaders: Marie Castets & Jean Yves Blay
The CASTETS/BLAY team aims to understand the relations and dynamic evolution of tumor niche in pediatric cancers.

Cellular Senescence, Cancer and Aging

Team leader: David Bernard
The BERNARD team aims to decipher how senescent normal and cancer cells, in particular through their secretome, communicate with the neighborhood and impact tumor progression and resistance.

Glioblastoma metabolism and heterogeneity, in 3D organoids

Team leader: Erika Cosset
The COSSET team aims to understand how GBM heterogeneity generates a “tumor ecosystem” that induces a stress-tolerant state and adaptation in response to various tumor microenvironmental stresses.

Cancer ecosystem dynamics, adaptation and modeling

Team leader: Pierre Saintigny
The SAINTIGNY team aims to combine mathematical modeling, computational and experimental biology to understand the evolution of the microenvironment spatial organization from normal to cancer and under the selective pressure of systemic therapy.

KidsCaN – Kids & Cancer Neuroscience

Team leader: Céline Delloye-Bourgeois
The DELLOYE-BOURGEOIS team studies the multilayered dialogs between pediatric cancer cells and the growing tissues in which childhood tumors arise and metastasize. They are particularly interested in the capacity of some cancer cells to integrate into cellular networks with the microenvironment.

Reprogramming, stem cells and oncogenesis

Team leader: Fabrice Lavial
The LAVIAL team explores how embryonic factors and pathways are reactivated during tumorigenesis to promote cellular plasticity and heterogeneity.

Ribosome, translation and cancer

Team leader: Jean-Jacques Diaz
The DIAZ team aims to determine the role of epitranscriptomic (i.e., chemical modification of ribosomal RNA) in driving glioblastoma heterogeneity and remotely preparing the pre-metastatic niche in breast cancer.

Antigen presentation, T-cells and cancer

Team leaders : Stéphane Depil et Jenny Valladeau-Guilemond
The DEPIL/VALLADEAU team aims is develop new immunotherapies through the identification of new tumor antigens, pathways and molecules enhancing antigen presentation within the tumor, and T cell engineering. In this context, a better understanding of the tumor heterogeneity is absolutely needed.