M2 internship position in cancer immunology: Tissue resident CD8+ T cells and dendritic cells in lung cancer.

Tissue resident CD8⁺ T cells and dendritic cells in lung cancer.

A 6 months 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 (https://www.guermonprezlab.org).

Project
Lung tissue resident memory CD8⁺ T lymphocytes (T_RMs) represent a population of cytotoxic lymphocytes able to provide frontline immunity against respiratory infections. There is strong evidence that lung cancer (NSCLC) infiltration by CD8⁺ T_RMs is associated with favorable clinical outcomes and improved responses to immune checkpoint blockade immunotherapies. Despite their clinical relevance, the mechanisms underlying the activation and maintenance of T_RMs remain ill-defined.

The main objective of this project is to understand the impact of dendritic cell populations on the infiltration of lung cancer by CD8⁺ T_RMs during lung cancer development. This analysis will be primarily developed in a pre-clinical model of lung adenocarcinoma.

Specifically, the project intends:

1. To disentangle the developmental relationship between resident and exhausted tumor-infiltrating CD8+ T lymphocytes.
2. To analyse the role of DCs on the establishment and maintenance of CD8⁺ T_RMs in using genetic tools to manipulate DCs populations or function.

The approaches to be implemented involve high dimensional characterization of lung cancer CD8⁺ T_RMs and single cell analysis of CD8⁺ T cell fate in lung cancer model.

Experimental approaches
1. Murine model of lung cancer (KrasG12D, p53ko).
2. Murine models of dendritic cell deficiency.
3. Adoptive transfer of transgenic CD8 T cells.
4. High dimensional flow cytometry.
5. CRISPR Cas9
6. Bulk RNAseq and scRNAseq.

Candidate profile
We are looking for highly motivated individuals willing to bring new insights into the biology of adaptive immunity against cancer with a strong emphasis on dendritic cell-T cell interactions.

Contact & applications
Pre-application, informal inquiries are welcome. For applications, please send to pierre.guermonprez@pasteur.fr one CV, a publication list, a cover letter and the email contact for 2 references.