Immunity and Cancer

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.

Immunity and Cancer | Daniel Olive

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.

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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.

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Viruses and Cancer | Ivan Hirsch

We investigate interactions of human oncogenic viruses (particularly of hepatitis C virus, HCV, the etiologic agent of hepatocellular carcinoma), with the innate immunity system (cf publication "Impaired Toll-like receptor 7 and 9 signaling: from chronic viral infections to cancer") and the virus escape from its control (cf publication "Activating NK cell receptor expression/function (NKp30, NKp46, DNAM-1) during chronic viraemic HCV infection is associated with the outcome of combined treatment").

 

The elimination of HCV in more than 50% of chronically infected patients by treatment with interferon-∝ (IFN-∝ suggests that plasmacytoid dendritic cells (pDCs), major producers of IFN-∝, play a central role in mechanisms, which govern viral persistence (cf publication "Hepatitis C virus is a weak inducer of interferon alpha in plasmacytoid dendritic cells in comparison with influenza and human herpesvirus type-1").

In collaboration with the « Lymphocyte activation Group », we deciphered the intracellular signaling mechanisms triggered by HCV in pDCs (cf publications "Hepatitis C virus fails to activate NF-κB signaling in plasmacytoid dendritic cells" & "HCV glycoprotein E2 is a novel BDCA-2 ligand and acts as an inhibitor of IFN production by plasmacytoid dendritic cells" ).

Exposure of pDCs to cell-free or cell-associated HCV results in totally different outcomes – activation or suppression of the principal pDC function, type I and III IFN production. Inhibitors of signaling pathways will be used to modulate these functions.

In view of the central role of pDCs in regulating the immune system, we expect that our results will provide insight into the role of HCV-pDC interaction in HCV immune evasion, and will improve our understanding of the mechanisms leading to the establishment of chronic HCV infection. Better understanding of these mechanisms can improve present anti-viral therapy.

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Human NK cell development and effector functions in Health and disease | Cyril Fauriat

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.

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Microenvironment and immunological signaling in malignant lymphoproliferations | Luc Xerri

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).

 

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Allogenic Immunotherapy | Didier Blaise

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 :

  1. Therapeutic vaccines using WT1 protein and adjuvant
  2. Infusion of donor NK cells following in vitro activation
  3. Infusion of anti-KIR mAb to relase the inhibition of NK cells in patients post aSCT
  4. 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.

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CDD de 18 mois ingénieur/post doctorant en immunité tumorale

An engineer/ post-doctoral position in Tumor Immunology is available in the team of Daniel Olive in  the Cancer Research Center of Marseille (CRCM) INSERM-U1068, located at the Institut Paoli Calmettes in Marseille.

The position is funded for 18 months that could be extended by INSERM TRANSFERT  (research contract with Glaxo Smith Kline) with a salary commensurate with candidate experience.

The candidate will develop ex vivo studies on tumor samples and in vivo models dedicated to the function of a novel cosignaling pathway involved in escape mechanisms in cancer (lymphomas, leukemias and solid tumors)

The study will be performed between the immunity and cancer lab, the biopathology department and clinical units

Applicants should be highly motivated with an excellent experience in immunology, mAbs, flow cytometry and if possible animal models.

Start date: December 2015

To apply please send a CV including contact details of 3 references and a

cover/motivation letter and a short summary of your current researches and center of scientific interest  by E-mail to:daniel.olive@inserm.fr