Luxembourg Institute of Health (LIH) is the leading public research center in Luxembourg for basic, pre-clinical and clinical research in biomedicine and public health.
Our clinically-oriented biomedical research activities in Oncology, Infection & Immunity and Population Health encompass the generation of knowledge on the pathogenesis, diagnosis and treatment of diseases with large impacts on public health and the epidemiological surveillance of these diseases.
With the mission to deliver scientific, economic and societal value for Luxembourg, LIH aims to translate knowledge into clinical applications impacting on healthcare systems while shaping personalized medicine.
Recently, we demonstrated in vitro that a subpopulation of breast cancer cells responds to natural killer cell attack with a quick and massive accumulation of actin in the region of the immunological synapse, a process we called the "actin response".
Inhibition of the actin response was sufficient to convert resistant breast cancer cells into a highly susceptible phenotype.
From a mechanistic standpoint, we found that the actin response protects target cells from apoptosis by decreasing intracellular levels of a key cytotoxic protease, namely granzyme B, secreted by natural killer cells.
Our pioneering study on the role of actin cytoskeleton in tumor immune evasion has been published in Cancer Research (Al Absi et al.
2018 Cancer Research. 78 : 5631-5643).
You will work on a newly process that protects tumor cells against cytotoxic lymphocytes (NK and CD8+ T cells). The experimental work will focus on two main axes : 1) validation of our in vitro data in mouse models (both natural killer and cytotoxic T cells’ contributions will be considered) and 2) identification of clinically-relevant targets to inhibit the actin response (in collaboration with the proteomic platform of LIH).
The goal is to provide a solid ground for translating our pioneering data on actin-driven immune evasion into innovative clinical applications aimed at restoring an effective anti-tumor response and / or to improving the efficacy of current immunotherapies.
Dr. Clément Thomas :
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