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Allocation

A 4 year PhD student

University faculty : Sciences
Department : NARILIS
Starting date : 10/1/2019
Category : scientific personnel
Allocation : External funds

Responsabilities

The radiobiology group of NARILIS from the University of Namur is recruiting a 4 year PhD student.

Research project: Tumor immunosuppression modulation by proton irradiation in order to boost the anti-PD-1 immune checkpoint blocker effects.

Treatment of head and neck squamous cell carcinoma (HNSCC) remains challenging and survival rates remain stagnant. Recent clinical trials have demonstrated promising results with immune checkpoint blockers but their success is mitigated by the immunosuppressive properties of the tumor microenvironment. Tumor-associated macrophages (TAMs) represent the most important immune cell compartment in tumor and more than 70% of them are M2-like macrophages with efficient immunosuppressive activities. Therefore, retuning of TAM to M1 phenotype, competent for T cell activation, would be a key for effective immunotherapy. Radiotherapy based on X rays has been demonstrated to improve tumor immune rejection both by inducing immunogenic cell death but also by affecting myeloid cells. We recently showed that protontheraou can influence macrophage phenotype in vitro (Genard et al, 2018). However, few dta are available regarding the immune effects of protontherapy in vivo. In this work, we will systematically compare both types of irradiation using modulate the tumor immunosuppressive environment and investigate its possible synergy with immunotherapy for tumor eradication. These results will be completed in vitro and in vivo and the combination with anti-PD-1 treatment in vivo will be investigated. In addition to tumor size and survival, different parameters will be studied, notably the number and the phenotype of macrophages and T cells within the tumors, using single cell RNA seq, the abundance of immunosuppressive and immunostimulating cytokines and the apoptosis of cancer cells. The results may guide precision medicine approaches by revealing tumor microenvironment components that influence treatment responses.

Profile

Master 120 in Biochemistry, Cell Biology or Chemistry with a strong background in cancer molecular biology. A knowledge in radiobiology and/or cancer immunology is a strong asset.

The candidate must be highly motivated, inquisitive and self-driven. He/she should be team-spirited since this project will be developed in close collaboration with Profs. S. Lucas and A-C. Heuskin (UNamur, department of Physics).

Additional information

Prof. Carine MICHIELS, URBC-NARILIS

University of Namur, 61 rue de Bruxelles, 5000 Namur, Belgium - Tel.: +32 81-724131.

Remarks

Financial support: This project is financed by a Télévie grant from the FNRS.

Procedure

Applications with a detailed CV should be sent to Prof. Carine MICHIELS (carine.michiels@unamur.be) before August 14, 2019.