Dr Christine Bezombes

PDLS at the heart of the identification of

new therapeutic targets in NHL

 

The research topic of 3DLNH group managed by C. Bezombes focuses on the biological characterization of non-Hodgkin’s lymphoma (NHL), the identification of immuno-escape mechanisms and their targeting within 3D culture models.

These models set up from cell lines called MALC (Multicellular Aggregates of Lymphoma Cells) in a first step by the inverted drop technique present a spatial architecture but also transcriptomic and protein profiles and a response to treatment closer to what is observed in patients compared to cell cultures in suspension. Using co-culture systems with Tgd lymphocytes or NK cells, it is then possible to evaluate not only the infiltration of immune cells within tumor masses using 3D imaging, but also to study the mechanisms of action of different therapeutic antibodies or to evaluate the targeting of immune checkpoints in the antitumor response. However, neither the inverted drop technique nor the use of cell lines are adapted to therapeutic screening in human pathology models. Thus, based on recently developed method and new tools allowing a fully and in-depth characterization, we are now able to establish 3D models from NHL samples integrating the tumor microenvironment. These models, called PDLS for Patient Derived Lymphoma Spheroid, are relevant preclinical models allowing to: i) explore the biology of NHL, ii) identify the immune escape mechanisms that characterize them and iii) evaluate the efficacy of targeted therapies. Altogether, we believe that results obtained with PDLS, integrated with datas of full body imaging, transcriptomic analysis and clinical datas of the same patients, will allow to go further in the development of personalized therapy.

     

    Technologies developed:

    3D culture (patient lines and cells), 2D and 3D imaging (Operetta, confocal, Incucyte, SPIM), immunohistochemistry, multiparametric flow cytometry (more than 10 markers), spatial transcriptomics (to be developed)

     

    Partners and funding:

    • THERVALINFO/POCTEFA
    • CATALY/Ligue contre le cancer
    • LTGDARME/ DEFI CLE region
    • BIALYMPH/TRANSCAN
    • CIELYM/Incyte
    • TALYIES/ROCHE

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