Thanks to anticancer immunotherapies targeting immune checkpoints, the proportion of patients with metastatic melanoma (MM) in remission after 5 years has tripled during the last years. However, therapeutic options are sparse for patients who do not respond to immunotherapy or who relapse after remission (40% and 20%, respectively). One of the current challenges is therefore to understand the molecular mechanisms associated to resistance in order to adapt the therapeutic strategy.

Team 4 of the Cancer Research Center of Toulouse (CRCT, led by Prof. Thierry Levade and Dr. Nathalie Andrieu) has recently discovered that some tumor lipids, belonging to the class of sphingolipids, contribute to the progression of melanomas by promoting cancer immune escape.

From these observations, the team has set up a European research program coordinated by Dr Nathalie Andrieu, and for which the two main objectives are:

1. To evaluate the combination of immunotherapies, already used in the clinic against melanomas, and therapies targeting the production of tumor sphingolipids. To this end, Team 4 of the CRCT is working in close collaboration with the teams of Dr. Jean-Christophe Marine (VIB, Leuven, Belgium) and Dr. Luisa Lanfrancone (IEO, Milan, Italy), who are developing preclinical models of melanoma to monitor the efficacy of these new therapeutic combinations.
2. To identify whether some tumor or circulating lipids are predictive biomarkers of the efficacy of immunotherapies in patients with MM. This work will lead to the opening of the “IMMUSPHINX” clinical trial at the University Cancer Institute of Toulouse-Oncopole (IUCT-O), under the supervision of Prof. Nicolas Meyer (University Hospital of Toulouse) in 2018. The aim is to connect the responses to immunotherapies with the tumor and circulating lipid parameters in patients with MM. This study will be carried out in close collaboration with IUCT-O’s Pathology and Biostatistics departments. It will be supplemented by data from the Oncodermatology departments of Prof. Brigitte Dreno (University Hospital of Nantes) and Prof. Susana Puig (University Hospital of Barcelona).

The IMMUSPHINX project is funded by the European translational cancer research network ERA-NET TRANSCAN and supported over 3 years (2017-2020) by the Fondation ARC pour la Recherche sur le Cancer for the French teams participating in the project. It is an essential step in determining whether it is possible to expand the use and effectiveness of current immunotherapies to additional patients with MM and possibly other cancers.

Patents associated to this project:

• Methods and pharmaceutical compositions for enhancing CD8+ T cell-dependent immune responses in subjects suffering from cancer. WO 2017134116 A1
• Methods for enhancing the potency of the immune checkpoint inhibitors. WO 2017129769 A1
• Methods for predicting the survival time of patients suffering from cancer. EP 16306138.5. et EP 16306139.3.
• Use of sphingosine kinase 1 as biomarker for predicting response to immune-checkpoint inhibitors. EP 18305178.8