Characterization of Renal Cell Carcinoma Heterotypic 3D Co-Cultures with Immune Cell Subsets

Article Article scientifique Article Characterization of Renal Cell Carcinoma Heterotypic 3D Co-Cultures with Immune Cell Subsets eng 2021-05-22 2021-05-22 author Rausch Magdalena 0000-0002-8485-9220 897516 author Blanc Léa 0000-0002-0289-6934 855964 author De Souza Silva Olga 0000-0002-1314-536X author Dormond Olivier 0000-0002-6418-1782 author Griffioen Arjan W. author Nowak-Sliwinska Patrycja 0000-0002-8299-0444 848409 2551 10.3390/cancers13112551 34067456 2072-6694 PMC8197009 https://www.mdpi.com/2072-6694/13/11/2551 <p>Two-dimensional cell culture-based platforms are easy and reproducible, however, they do not resemble the heterotypic cell-cell interactions or the complex tumor microenvironment. These parameters influence the treatment response and the cancer cell fate. Platforms to study the efficacy of anti-cancer treatments and their impact on the tumor microenvironment are currently being developed. In this study, we established robust, reproducible, and easy-to-use short-term spheroid cultures to mimic clear cell renal cell carcinoma (ccRCC). These 3D co-cultures included human endothelial cells, fibroblasts, immune cell subsets, and ccRCC cell lines, both parental and sunitinib-resistant. During spheroid formation, cells induce the production and secretion of the extracellular matrix. We monitored immune cell infiltration, surface protein expression, and the response to a treatment showing that the immune cells infiltrated the spheroid co-cultures within 6 h. Treatment with an optimized drug combination or the small molecule-based targeted drug sunitinib increased immune cell infiltration significantly. Assessing the therapeutic potential of this drug combination in this platform, we revealed that the expression of PD-L1 increased in 3D co-cultures. The cost- and time-effective establishment of our 3D co-culture model and its application as a pre-clinical drug screening platform can facilitate the treatment validation and clinical translation.</p> 3D co-cultures PD-L1 Combination therapy Heterotypic spheroids Immune cells Immunotherapy Infiltration Renal cell carcinoma Sunitinib Dewey 615 31 Section des sciences pharmaceutiques 17 false 881 Sciences analytiques Cancers 13 11 85a24c35-af62-45b5-b0d0-730da6016d74 Article (Published version) Public cancers-13-02551-v3.pdf 2577504 application/pdf CC BY-4.0 openAccess Faculté des sciences / Section des sciences pharmaceutiques

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Characterization of Renal Cell Carcinoma Heterotypic 3D Co-Cultures with Immune Cell Subsets	Cancers			2021	175	405

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Blanc, Léa