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Single cell mapping of the vasculature in aggressive B lymphomas and topological interactions with CD8 T cells and Gamma-delta T Cells

Starting date:

October 1st 2021

Duration:

36 months

Location:

A PhD student position funded for 3 years by the LABEX TOUCAN (‘Laboratoire d’Excellence Toulouse Cancer’; https://www.crct-inserm.fr/labex-toucan/) is available in the Teams of Jean-Philippe GIRARD (IPBS, CNRS and University of Toulouse, France ; http://www.ipbs.fr/vascular-biology-endothelial-cells-immunity-inflammation-and-cancer) and Camille LAURENT (CRCT, Inserm and University of Toulouse; https://www.crct-inserm.fr/09-j-j-fournie/ ).

 

The PhD student will be administratively attached to the IPBS but will work in both laboratories (IPBS and CRCT). IPBS (http://www.ipbs.fr ) and CRCT (https://www.crct-inserm.fr ) are two large Research Centers from CNRS, Inserm and University of Toulouse. All the necessary biological resources and research facilities, including state of the art technological facilities, will be available.

Abstract:

Immunity plays an important role in cancer control, notably with highly mutated tumours such as Diffuse Large B-cell Lymphoma (DLBCL), an aggressive (fast-growing) non-Hodgkin lymphoma that affects B cells. Indeed, CD8 T cells and gamma-delta T cells display potent antitumour cytotoxicity and are specifically reactive to lymphomas. DLBCL often develops in the lymph nodes. High endothelial venules (HEVs) are specialized blood vessels for lymphocyte entry into lymph nodes. HEVs may thus play an important role in the recruitment of CD8 T cells and gamma-delta T lymphocytes in DLBCL lymph nodes.

The major objective of the project is to perform single cell mapping and spatial transcriptomics (ST) to characterize the density, maturation and functional status of HEV endothelial cells (MECA-79+CD31+) and non-HEV endothelial cells (MECA-79-CD31+), and define their topological interactions with cytotoxic gamma-delta T cells and CD8 T cells in DLBCL patient’s biopsies. The project will greatly benefit from the expertise of:

       - Jean-Philippe Girard’s team (IPBS) on HEV blood vessels, scRNASeq analyses of endothelial cells, and HEV-mediated lymphocyte recruitment in lymph nodes (Moussion and Girard, Nature 2011; Girard et al., Nat Rev Immunol 2012; Lafouresse et al., Blood 2015; Veerman et al., Cell Rep 2019), and

       - Camille Laurent’s team (CRCT) on human B cell lymphomas (Laurent et al., Blood. 2020; Laurent et al., J Clin Oncol. 2017; Laurent et al., Blood. 2011), cytotoxic T cells, single cell RNA sequencing (scRNASeq, CITEseq) (Pizzolato et al., PNAS 2019; Pont et al., Nucleic Acids Res 2019) and spatial transcriptomics (transcriptomic hallmarks of all cells in a lymphoma biopsy in situ).

This study will deeply increase our knowledge about the distribution and functional status of HEV and non-HEV endothelial cells, gamma-delta and other cytolytic T cells infiltrating human lymphomas. It may have important clinical consequences such as the identification of new predictive biomarkers, and guide T cell-based immunotherapies currently developed in Comprehensive Cancer Centers worldwide.

Keywords:

aggressive B lymphoma, high endothelial venule, endothelial cell, spatial transcriptomics, scRNA-seq, anti-tumor immunity

Additional Information

Requirement: Master's degree in Cancerology, Immunology, Vascular Biology or Molecular Biology. Experience in transcriptomics (RNA-seq or scRNA-seq) and/or bioinformatics would be a plus. We are looking for a creative and highly motivated PhD student strongly committed to research. Joint PhD supervisors: Drs Jean-Philippe Girard (Inserm Research Director at IPBS) and Camille Laurent (MCU-PH at CRCT).

 

How to apply:

Please, send your application (in French or English, including a motivation letter, curriculum vitae, and rankings in University Licence/Master or Engineering school) to jean-philippe.girard@ipbs.fr and laurent.c@chu-toulouse.fr  (Deadline: the position will remain open until filled; only successful applicant will be contacted).