Metabolites and enzymes of ceramide metabolism as biomarkers of resistance to immunotherapies ?

Pr Nicolas Meyer
Associate investigators : Drs Nathalie Andrieu, Céline Colacios, Anne Montfort et Pr Bruno Ségui

Our team is involved in 2 complementary clinical studies: MELANFα (NCT03348891) and IMMUSPHINX (NCT03627026), two translational interventional studies evaluating predictive biomarkers of resistance to nivolumab +/- ipilimumab in tumour biopsies and plasma of 120 patients with metastatic melanoma. Blood samples and tumour biopsies are collected before and after induction of immunotherapies.

We hypothesise that immune and sphingolipid signatures can predict response/resistance to ICIs in melanoma patients. For both clinical trials, we are studying during treatment the immune response in blood as well as the sphingolipidome in plasma (by mass spectrometry) and the expression of ceramide metabolism enzymes in tumours.

Funding :

Funding: Bristol-Myers Squibb; Association pour la Recherche sur le Cancer; Fondation Toulouse Cancer Santé

Une forte expression de la sphingosine kinase 1 dans les biopsies de mélanome prédit la résistance au traitement par anti-PD-1 chez les patients atteints de mélanome avancé (extrait d’Imbert et al., Nat. Commun. 2020). / High sphingosine kinase 1 expression in melanoma samples predicts resistance to anti-PD-1 therapy in advanced melanoma patients (From Imbert et al., Nat. Commun. 2020)