Postdoctoral Fellow in Tumor Immune Evasion - CT0320

Immune evasion is a hallmark of cancer progression and represents a major hurdle to the design of effective therapeutic strategies. We recently uncovered a widely conserved mechanism by which resistant tumor cells respond to immune effector cell attack. The ACTIVASION project aims at exploring how this mechanism (i.e. fast remodeling of the tumor cell actin cytoskeleton) alters the structure and the function of the immunological synapse, the cell-cell interaction interface used by immune cells to recognize and kill target cancer cells.
84, rue Val Fleuri, Luxembourg L-1526, Luxembourg
20/03/2020 18:13:13

The project

A better understanding of the fundamental mechanisms underlying tumor immune evasion is critically for the development of new immunotherapy strategies aimed to restore/stimulate effective antitumor immune response in a larger number of patients. We previously reported a pivotal role for the actin cytoskeleton in mediating cancer cell resistance to natural killer (NK) cell-induced cell death (Al Absi et al., 2018 Cancer Research. 78: 5631-5643). We showed that, upon NK cell attack, a massive accumulation of actin near the immunological synapse (the interface between the NK cell and its target) rapidly takes place in resistant tumor cells. We termed this process "actin response" and provided evidence that it protects NK cell-conjugated target cells from undergoing apoptosis by preventing intracellular accumulation of NK cell-secreted cytotoxic molecules. Recently, we established that the actin response is a fundamental feature of immune evasion conserved across different malignancies and induced in response to AG-specific cytotoxic T lymphocyte attack. However, the mechanism underlying actin response-mediated immune evasion remains unclear. Based on our unpublished data, we will explore the possibility that the actin response acts as a "physical barrier" altering the structure and activity of the immunological synapse. Using state-of-the-art live cell imaging approaches, we will depict the structural and functional immunological defects caused by the actin response during the early steps of immune effector cell-tumor cell interaction, such as alterations of the immunological synapse organization and increase of inhibitory immune checkpoint molecule density at the cell-cell contact points. Finally, we aim at examining the prevalence of the actin response in pathological samples.


    Research environment

    The Cytoskeleton and Cancer Progression (CCP) group  belongs to the Department of Oncology, whose activities focus on the cellular and molecular mechanisms of tumor progression using a wide range of cutting edge technologies, including genomic, transcriptomic and proteomic analyses, and in vitro and in vivo imaging modalities as well as state-of-the art animal models for cancer research. The CCP group focuses on actin regulatory proteins and related signaling pathways driving tumor cell invasion and immune evasion, with the goal to identify new prognostic markers and therapeutic targets. We combine biochemistry, cell biology, reverse-genetics and advanced live-cell imaging approaches as well as mouse models of breast cancer metastasis.


    KEY accountabilities
    • Carry out a research project independently (drafting, validation, etc.) and set up follow up projects.
    • Participate in the execution of a research project (implementation, follow-up, planning) within a research team while trying to optimize productivity.
    • Participate in the activities of the research unit and integrate into teams.
    • Design and execute experiments as required by the project.
    • Write scientific articles for peer-reviewed international journals.
    • Develop scientific methodology and techniques adapted to the research project.
    • Contribute to defining research priorities with the Director of the Department.
    • Evaluate research results for patent filing together with BDO and the Director of the Department.
    • Establish an internal and external cooperation for the implementation of new laboratory techniques.
    • Present the work as well as results during research unit meetings and at international meetings, congresses.
    • Establish and disseminate the bibliography to the other researchers, students and technicians.
    • Communicate problems and suggestions for possible solutions in a clear way.
    • Stay updated with the current scientific literature concerning the study.
    • Participate in the societal dimension: dissemination of simplified research results to the general public (through articles, conferences, etc.).

    KEY SKILLS, EXPERIENCE AND QUALIFICATIONS
    • Successful PhD or previous Post-Doctoral position in the area of immunology (ideally onco-immunology).
    • Hands-on experience in experimental lab work using immune and cancer cell models.
    • Solid experience in (imaging) flow cytometry.
    • Experience in animal experimentation and protocols related to the project, i.e. immune system and/or cancer.
    • Excellent planning and communication skills, able to work in a complex team and to coordinate work.
    • Fluency in English is mandatory.

     
    REF.: CM/PDFTIE0320/CT/CCP
    2 year fixed-term contract - Full time - Start in June 2020

    More INfo

    Please contact: Dr Clément THOMAS
    clement.thomas@lih.lu

    Website: https://ccp.lih.lu/cytoskeleton-and-cancer-progression