Reprogramming ceramide metabolism to overcome resistance to immunotherapies

Drs Céline Colacios et Anne Montfort
Associate Investigators : Dr Nathalie Andrieu, Prs Thierry Levade, Bruno Ségui, Laurent Nieto

Our recent work shows that alterations in ceramide metabolism in melanoma cells contribute to tumour resistance to ICI. We are studying the nature of the molecular mechanisms involved in this process and in particular those controlling immune escape. In addition, we aim to determine the best strategies for reprogramming ceramide metabolism to overcome melanoma resistance to ICI. We will evaluate whether inhibitors of ceramide metabolism enzymes, aimed at reducing S1P levels and increasing ceramide levels, improve the efficacy of ICIs in mouse models of melanoma.

Funding:

Association pour la Recherche sur le Cancer; Toulouse Cancer Santé Foundation; Sanofi-Genzyme, Bristol-Myers Squibb Foundation

Illustration :

Signature lymphoïde enrichie dans les tumeurs exprimant fortement la sphingomyélinase neutre 2 (Extrait de Montfort et al., Cancer Immunol. Res. 2021) / Enriched lymphoid signature in tumours expressing neutral sphingomyelinase 2 at high levels (from Montfort et al., Cancer Immunol. Res. 2021)