The slice assay: a new preclinical model to monitor T cell activity in human tissues

Presentation of the tissue slice assay

The team has set up a novel experimental system of tissue slices which, combined to dynamic imaging, enables the visualization and tracking of T cells in murine and human tissues, including tumors.  

The tumor slice assay for monitoring T cell activities by video fluorescence microscopy in a preserved tumor microenvironment. Fluorescently labeled T cells are plated onto thick slices prepared from a human tumor biopsy. The localization, migration and activation of the plated T cells are then evaluated

This approach offers a number of possibilities:

•     Evaluating the effects of novel immunotherapy

•     Screening for therapeutic molecules able to restore T cell migration within tumors

•     Monitoring the efficacy of CAR T cells and improving their therapeutic value

•    Testing the toxicity of immunotherapy

Past and ongoing projects using the tissue slice assay

-    Monitoring of T cells in human tumors and demonstration of a negative influence of the extracellular matrix and macrophages on lymphocyte migration (Salmon, J. Clin. Invest. 2012) (http://www.ncbi.nlm.nih.gov/pubmed/22293174), (Peranzoni, PNAS 2018) (http://www.ncbi.nlm.nih.gov/pubmed/29632196)
 
(TISSUE SLICE Web Movie 1)
-    Monitoring of plasma cells in murine lymph nodes (collaboration with Dr. Sanjiv Luther, University of Lausanne) (Huang et al. PNAS 2018) (http://www.ncbi.nlm.nih.gov/pubmed/29967180)
-    
 
(TISSUE SLICE Web Movie 2)

-    Monitoring of CAR T cells in human tumors

 
(TISSUE SLICE Web Movie 3)

-    Monitoring of follicular helper T cells in human lymphoid tissues (collaboration with Pr. Martin-Leo Hansmann, University of Frankfurt)


(TISSUE SLICE Web Movie 4)

Know-how publications

Donnadieu E, Michel Y, Hansmann ML (2019) Live Imaging of Resident T-Cell Migration in Human Lymphoid Tissue Slices Using Confocal Microscopy. Methods in molecular biology 1930:75-82. (http://www.ncbi.nlm.nih.gov/pubmed/30610601)

Peranzoni E, Bougherara H, Barrin S, Mansuet-Lupo A, Alifano M, Damotte D, Donnadieu E (2017) Ex Vivo Imaging of Resident CD8 T Lymphocytes in Human Lung Tumor Slices Using Confocal Microscopy. Journal of visualized experiments : JoVE (130).
https://www.jove.com/video/55709/ex-vivo-imaging-resident-cd8-t-lymphocytes-human-lung-tumor-slices

Salmon, H., A. Rivas-Caicedo, F. Asperti-Boursin, C. Lebugle, P. Bourdoncle, and E. Donnadieu. (2011). Ex vivo imaging of T cells in murine lymph node slices with widefield and confocal microscopes. JoVE (53).
http://www.jove.com/video/3054/ex-vivo-imaging-t-cells-murine-lymph-node-slices-with-widefield

Contacts:

If this approach is of interest for your projects, please contact us. Technology transfer has been done with many academic labs in France and in Europe that routinely employ the “slice assay”.

emmanuel.donnadieu@inserm.fr – Tel : +33 1 40 51 65 64
lene.vimeux@inserm.fr