Deciphering the role of intra-tumoral dendritic cells in the dynamic control
of CD4+ and CD8+ lymphocytes in lung cancer.
A 3-year, post-doctoral position is available in the Guermonprez lab at Institut Pasteur Paris (“Dendritic cells and adaptive immunity” Unit, Immunology Department https://research.pasteur.fr/fr/department/immunology/). The Guermonprez lab investigates the role of dendritic cell subsets in regulating T cell responses and explores novel immunotherapeutic approaches (https://www.guermonprezlab.org). The Guermonprez lab has recently identified a novel DC population with distinct contribution to T cell immunity both in human and mice. Current burning questions of the lab are to understand the contribution of these new DC subsets to anti-tumor T cell immunity and how to harness these subsets for cancer immunotherapy.
There is strong evidence that some populations of CD8+ T cells like tissue resident memory-like (TRMs) or poorly differentiated stem-like precursors of exhausted cells (TPEX) are associated with favorable clinical outcomes and improved responses to immune checkpoint blockade immunotherapies. However, the anti-tumoral function of CD8+ T cells against lung cancer is severely curtailed by immunosuppressive features of the tumor microenvironment including the onset of T cell exhaustion. CD4+ T cell help can potentially reactivate the generation of effectors from stem-like cells but this response is somehow impaired.
Main objectives
1. To analyse the spatial organization of the interactions between DCs, CD8+ T and CD4+ cells within the tumor micro-environment. Single cell approaches will be integrated with spatial transcriptomics and high dimensional imaging to decipher the transcriptional phenotype of interacting DCs and T lymphocytes. Existing and novel murine genetic tools will be implemented to perturb and analyse the functional outcomes of these interactions.
2. To uncover novel actionable pathways controlling the ability of dendritic cells to (re-)activate the effector function of CD8+ tumor-infiltrating T cells via CD4+ T cell help. Novel immunotherapeutic approaches based on recombinant antibody production or mRNA-containing lipid nanoparticles will be evaluated.
The project will be primarily developed in a pre-clinical murine models of lung adenocarcinoma.
Missions
1. Design experiments and formalize experimental protocols.
2. Organize and conduct wet bench experiments in pre-clinical models of cancer involving animal experimentation.
3. Analyze experimental data and keep organized data archives in compliance with local policies.
4. Participate actively to student co-supervision.
5. Interact and collaborate productively with other researchers within and outside of the team, including bioinformatic engineers.
6. Present data in lab meetings and communicate research outputs in scientific meetings.
7. Participate actively to the production of manuscripts for publication.
Working environment
The Guermonprez lab is located on the Institut Pasteur historical campus, in central Paris (75015) and affiliated to the Immunology Department and the Stem cell and developmental biology CNRS UMR3738. The Institut Pasteur campus host a unique hub of multi-disciplinary research.
Research at the Institut Pasteur is based on 3 key strengths: research conducted at all levels of life, from molecules to individuals and populations; multidisciplinary strategies, focusing on molecular and cellular approaches as well as bioinformatics, biophysics, chemistry and nanotechnologies; unique technological facilities. Institut Pasteur is engaged on multiple fronts and its discoveries improve prevention, diagnosis and treatment of infectious diseases, neurodegenerative diseases, and cancers.
Candidate profile
We are looking for highly motivated individuals willing to bring new insights into the biology of adaptive immunity against cancer and spark innovation in cancer immunotherapy in pre-clinical settings. The successful candidate is expected to have:
- Project leadership, dynamism and eagerness to develop collaborative work.
- A PhD level (or other with substantial research experience, engineering schools e.g.).
- A former working experience and training in animal experimentation (mandatory).
- A solid scientific background in immunology (dendritic cells immunology, T lymphocyte immunology, airway immunology, cancer immunology…).
- A strong interest in cancer immunology.
Career development in academic research will be strongly encouraged and supported by the laboratory.
Contact
Pre-application, informal inquiries are welcome. For applications, please send to pierre.guermonprez@pasteur.fr one CV, a publication list, the email contact for 2 references.