Precision-Cut Tumor Tissue Slices as a Tool to Study the Tumor Microenvironment Interactions with Chimeric Antigen Receptor (CAR) T Cells v1

Le résumé fourni par la source

Up to date chimeric antigen receptor (CAR)-T cell therapy has been approved only for hematological malignancies, as CAR-T cells do not show comparable efficacy in solid tumors. Therefore, understanding the features of the tumor microenvironment (TME) is key to achieve improved efficacy of adoptive cell therapies (ACTs) against solid tumors. In this context, robust workflows dissecting the complex interactions between CAR-T cells and the TME are still lacking. To address this need, we have established an ex vivo workflow co-culturing tissue slices from patient tumor resections with CAR-T cells. We analyzed cytokine release via flow cytometry and cell infiltration into the tumor and stroma regions of the tissue slices using the MACSima™ imaging cyclic staining technology. Using this workflow, it is possible to observe the behavior of CAR-T cells within the tumor and its TME, as well as their infiltration in distinct tumor compartments. Assessment of ovarian carcinoma tissue slices revealed substantial release of specific cytokines and increased infiltration of T cells in the tumor areas when CAR-T cells were added to the tissue slices, compared to non-engineered T cells. The establishment of this novel approach will enable us to characterize the interaction between CAR-T cells and the TME. Nevertheless, as tissue slices present an intrinsic heterogeneity, we recommend the use of complementary models to verify the findings of this assay.

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