The Marseille Cancer Research Center celebrates its 50th anniversary ! -
The scientific activity is focused on immunology dedicated to cancer and chronic viral infections with the aim of developing a continuum leading from theoretical research to diagnostic and therapeutic applications. As a result of the scientific policy pursued by our team, a priority research direction has been established which involves studying the mechanisms used by cancer cells to escape surveillance systems (based mainly on the study of the immune deficiency associated to cancer with a major emphasis on innate immunity and cosignaling pathways).
The extensive involvement of pathologists and the strong collaborations with clinicians and surgeons help in achieving medical applications from the research work :
Illustration of the project which focuses on the biology of cytotoxic lymphocytes able to recognize and lyse tumor cells. CD8+ T cells play a major role in this process and are directly or indirectly assisted by other cytotoxic lymphocytes, such as NK cells and gamma-delta T cells. In the tumor microenvironment, these killer cells are regulated by other immune and stromal cells. Beyond the tumor site, many parameters grouped under the term “tumor macroenvironment” (or tumor organismal environment) can influence this anti-tumor response. In this context, different types of cancers are studied corresponding to the major axes developed at the Paoli-Calmettes Institute, a cancer comprehensive center that is part of the national Unicancer network: myeloid leukemia, breast and pancreatic cancers. For this, the work will be based on the activity of the Immunomonitoring platform closely linked to the team, allowing to draw up the most exhaustive panorama possible of the tumor microenvironment.
Our work analyzes the alterations of the innate immunity associated with cancer and viruses associated with cancer and the ways to circumvent them using biotherapies.
In addition, we investigate the functions of molecules belonging to the CD28/B7 (CD28, CTLA-4, PD-1, ICOS, BTLA and their ligands CD80, CD86, PD-L1, PD-L2 et ICOSL as well as the novel family BTN3A) and TNF/TNFR families (HVEM/TNFRSF14, LIGHT/TNFSF14) involved in the regulation of the immune system and that are major target for both immune subsversion but also new therapeutic strategies.
In T cells, our work focuses on the activation of a specific signaling pathway which turns-on upon T Cell Receptor (TCR) and costimulatory molecules triggering : the phosphatidyl-inositol 3’-kinase (PI-3K) signaling pathway, We are currently analyzing signaling pathways in other immune cell types such as NK cells. The PI-3K pathway has a role in many tumor types. In addition, we are investigating PI-3K functions in leukemic patients.
Our group is involved in the immunomodulation following allogenic stem cell transplantation (aSCT). Ongoing Phase 1 and 2 trials target the anti-tumor response during the 100 days following the aSCT such as :
Therapeutic vaccines using WT1 protein and adjuvant
Infusion of donor NK cells following in vitro activation
Infusion of anti-KIR mAb to relase the inhibition of NK cells in patients post aSCT
Administration of IMIDs such as revlimid.
We perform in parallel a comprehensive monitoring of immune reconstitution and of the surrogate markers associated to immuneintervention. Finally haploidentical transplantation regimen are underway.
The identification of biomarkers of response and toxicity is an important issue for optimising and personalising treatments for melanoma patients. Our main area of research concerns the identification of blood and tissue biomarkers of response and toxicity to immunotherapies in melanoma patients. We are analysing the impact of common biological variables and the evolution of different cell populations before and during treatment, using various techniques to characterise the phenotype of circulating immune populations and quantify soluble factors. We are also studying the tumour microenvironment using multiplex tissue analysis.
Carcinogenesis and tumor resistance to therapies are supported by strong metabolic modifications, which can be based on stressful conditions such as nutrient, oxidative or inflammatory stress. The hypothesis of my group is that mitochondria, involved in energetic metabolism and oxidative stress, are central in these processes.
The mitochondrial metabolism remains poorly explored in pancreatic cancer despite the central role of these organelles in cell bioenergetics and apoptosis. In that context, our project aims at exploring the impact of mitochondrial alterations in pancreatic cancer (PDAC) development and resistance to therapy.
Our first objective is to decipher mitochondrial features in PDAC tumors, to correlate them with tumor growth and therapeutic resistance, and to develop preclinical assays targeting mitochondria. This approach will contribute to the development of novel targeted cancer therapies and prevention of patient relapses.
Our second aim is to explore how nutritional interventions (physical activity and dietary components) can prevent mitochondrial alterations supporting tumor growth and therapeutic resistance.
Our third objective is to contribute to identify preventable risk factors for PDAC. Some are already well described: obesity, cigarette smoke and alcohol consumption. Epidemiological studies point to specific dietary factors included in Western-type diet (red and processed meat and sweetened beverages) and sedentary lifestyle as major risk factors for PDAC, but experimental studies are still missing to prove the causality.
Objectives 2 and 3 are conducted as part of the National Network NACRe (Réseau National Alimentation Cancer Recherche).
Notre équipe est impliquée dans des conseils d’administration de:
Team publications
Chretien AS, Fauriat C, Orlanducci F, Rey J, Borg GB, Gautherot E, Granjeaud S, Demerle C, Hamel JF, Cerwenka A, von Strandmann EP, Ifrah N, Lacombe C, Cornillet-Lefebvre P, Delaunay J, Toubert A, Arnoulet C, Vey N, Olive D
Rochigneux P, Lisberg A, Garcia A, Granjeaud S, Madroszyk A, Fattori S, Gonçalves A, Devillier R, Maby P, Salem N, Gorvel L, Chanez B, Gukasyan J, Carroll J, Goldman J, Chretien AS, Olive D, Garon EB
Fattori S, Le Roy A, Houacine J, Robert L, Abes R, Gorvel L, Granjeaud S, Rouvière MS, Ben Amara A, Boucherit N, Tarpin C, Pakradouni J, Charafe-Jauffret E, Houvenaeghel G, Lambaudie E, Bertucci F, Rochigneux P, Gonçalves A, Foussat A, Chrétien AS, Olive D
