CHRYSALIS

High grade serous ovarian cancer (HGSOC) is a highly aggressive pathology which requires new therapeutic strategies to improve patient outcome. Cancer treatment has taken a step forward with the advent of immunotherapy but has failed to be efficient in HGSOC. To overcome this, it is of importance to understand the tumor biology and take into account the whole tumor ecosystem, composed of tumor cells and their surrounding microenvironment. The tumor microenvironment (TME) includes different cell types. Cancer associated fibroblasts (CAF) and innate lymphoid cells (ILC) are abundant components of the TME. Interestingly, partners identified distinct CAF and ILC subpopulations in HGSOC and demonstrated that specific CAF and ILC subpopulations (CAF-S1 and ILCreg) display immunosuppressive activities by reducing T lymphocyte anti-tumor activity.

Based on solid preliminary data, we consider that CAF and ILC are able to inhibit, putatively in a synergic way, anti-tumor functions of several immune components. The immunosuppressive TME induced by these cells could explain the immunotherapy resistance observed in HGSOC patients.
To go further in CAF and ILC characterization in HGSOC leading to immunotherapy resistance, our research proposal will:
- Define how their diversity is generated
- Study all their interactions within the TME, especially with the immune component
- Develop a new diagnostic tool based on artificial intelligence (AI) to predict patient response to immunotherapy

To carry out our ambitious proposal, we'll use innovative technologies to study each cell individually and perform a fine tumors characterization in time and space. The strengths of our consortium reside in our complementary expertise and access to HGSOC patient cohorts. We aim to move toward translational clinic and provide to clinicians a new diagnostic tool to guide patient therapeutic strategy.