Immunotherapy is a treatment that aims to educate our immune system against cancer cells. This treatment resulted in a long-term response in patients with metastatic melanoma (40-60%) with in some cases total tumour regression. The challenge is now that the maximum number of patients can benefit from the progress of immunotherapy as quickly as possible. Our research team at the CRCT has shown that immunotherapy is less effective if certain tumour proteins are strongly expressed. These control the metabolism of sphingolipids, such as sphingosin kinase 1. Thus, our work has shown that the combination of treatments that block sphingosin kinase 1 with immunotherapy significantly increases therapeutic efficacy as well as survival in various pre-clinical cancer models (melanoma, breast and colon cancer). These major results have just been published in the scientific journal Nature Communication (Imbert et al.).
Our results, which highlight that sphingosin kinase 1 may be a predictive biomarker of immunotherapy response, led to the opening of the IMMUSPHINX clinical trial (NCT03627026) at the Toulouse-Oncopole University Cancer Institute (IUCT-O). This one is under the direction of Prof. Nicolas Meyer, oncodermatologist at the CHU in Toulouse. Its objective is to determine tumor and circulating lipid parameters and immunotherapy response criteria in patients with metastatic melanoma. This study is being carried out in close collaboration with the anatomopathology and biostatistics departments of the IUCT-O and the Pr group. Susana Puig (Hospital Clínic, Barcelona, Spain). It is also a bicentric study conducted with the oncodermatology department of Pr. Brigitte Dreno at the University of Nantes.
On the basis of these observations, the team set up a European research programme (ERA-Net-Transcan-2 H2020) coordinated by Dr Nathalie Andrieu and whose main objective is to evaluate the association of immunotherapies, already used in clinical practice against melanoma, to targeted therapies to modify the production of tumor sphingolipids. For this, the team works closely with the teams of Dr. Jean- Christophe Marine (VIB, Louvain, Belgium) and Dr. Luisa Lanfrancone (IEO, Milan, Italy), which develop preclinical models of melanoma to monitor the effectiveness of the treatments used.
Discover the published article :
Nat Commun. 2020 Jan 23;11(1):437
Resistance of melanoma to immune checkpoint inhibitors is overcome by targeting the sphingosine kinase-1.
Imbert C, Montfort A, Fraisse M, Marcheteau E, Gilhodes J, Martin E, Bertrand F, Marcellin M, Burlet-Schiltz O, Peredo AG, Garcia V, Carpentier S, Tartare-Deckert S, Brousset P, Rochaix P, Puisset F, Filleron T, Meyer N, Lamant L1, Levade T, Ségui B, Andrieu-Abadie N, Colacios C.
Collaborations :
Collaboration avec l’Institut Universitaire du Cancer de Toulouse- Oncopole (IUCT-O): Nicolas Meyer, Laurence Lamant, Philippe Rochaix, Pierre Brousset, Florent Puisset, Thomas Filleron, Elodie Anne Sylvie Martin, Julia Gilhodes.
Patent with Inserm Transfert :
- Use ok SK1 as biomarker for predicting response to immune checkpoint inhibitors. WO2019162325
- Methods for enhancing the potency of the immune checkpoint inhibitors. WO2017129769A1
Key words :
- Cancer,
- immunothérapy,
- métabolism,
- sphingosine kinase 1,
- résistance,
- lymphocytes T régulators
Contact :
Céline Colacios and Nathalie Andrieu
Team 4 CRCT
Mail : celine.colacios@inserm.fr nathalie.andrieu@inserm.fr
One picture :
