Our team integrate  the efforts of researchers in the field of Immunology and immunotherapy on the Cancer Research Center on the campus of the Institut Paoli-Calmettes, the anti-cancer centre of the Provence Alpes Côte d’Azur Region.

The Department’s scientific activity is focused entirely 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 pre-cancer including viral induced/associated cancers and 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 helps in achieving medical applications from the research work through the identification of new diagnostic or predictive markers and through developing innovative approaches to treatment aimed at restoring these protective responses.

Our projects
Immunity and Cancer

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.
 

Lymphocyte Activation

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.

Human NK cell development and effector functions in Health and disease

We study the biology of natural killer cells (NK) in healthy conditions and in the context of acute myeloid leukemia. In this condition, our team and others have shown that NK cells exhibited phenotypic and functional defects. By microarray analysis we have observed that genes involved in secretory pathways, protein synthesis and protein recycling were differentially expressed. We strive to understand the functions of these genes in the biology of NK cells both in terms of development and in terms of effector functions (cytotoxicity and secretion of cytokines and chemokines).

In parallel, we are interested in the development of human NK cells in pathological condition. Our model is the transplantation of hematopoietic stem cells. This study, done in constant interaction with the transplantation department of IPC led by Prof. Blaise, also a member of the Team, is used to support and provide insights for various clinical trials that have been developed at IPC or are under preparation.

Microenvironment and immunological signaling in malignant lymphoproliferations

Our major asset is the understanding of the pathogenesis of lymphoma and hodgkin diseases. We focus on the role of viruses and immunsuppressive mechanisms (cosignaling molecules).

Allogenic Immunotherapy

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.

Clinical and translational research in melanoma