Characterization of Renal Cell Carcinoma Heterotypic 3D Co-Cultures with Immune Cell Subsets
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-canc...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-05-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/11/2551 |
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| author | Magdalena Rausch Léa Blanc Olga De Souza Silva Olivier Dormond Arjan W. Griffioen Patrycja Nowak-Sliwinska |
| author_facet | Magdalena Rausch Léa Blanc Olga De Souza Silva Olivier Dormond Arjan W. Griffioen Patrycja Nowak-Sliwinska |
| author_sort | Magdalena Rausch |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T11:08:14Z |
| format | Article |
| id | doaj.art-528826a9444d4a479082d5e18d1f7707 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T11:08:14Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-528826a9444d4a479082d5e18d1f77072023-11-21T20:57:33ZengMDPI AGCancers2072-66942021-05-011311255110.3390/cancers13112551Characterization of Renal Cell Carcinoma Heterotypic 3D Co-Cultures with Immune Cell SubsetsMagdalena Rausch0Léa Blanc1Olga De Souza Silva2Olivier Dormond3Arjan W. Griffioen4Patrycja Nowak-Sliwinska5School of Pharmaceutical Sciences, Faculty of Science, University of Geneva, 1211 Geneva, SwitzerlandSchool of Pharmaceutical Sciences, Faculty of Science, University of Geneva, 1211 Geneva, SwitzerlandDepartment of Visceral Surgery, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, SwitzerlandDepartment of Visceral Surgery, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, SwitzerlandAngiogenesis Laboratory, Department of Medical Oncology, Amsterdam UMC, Vrije Universiteit Amsterdam, Medical Oncology, Cancer Center Amsterdam, 1081 HV Amsterdam, The NetherlandsSchool of Pharmaceutical Sciences, Faculty of Science, University of Geneva, 1211 Geneva, SwitzerlandTwo-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.https://www.mdpi.com/2072-6694/13/11/25513D co-culturescombination therapyheterotypic spheroidsimmune cellsimmunotherapyinfiltration |
| spellingShingle | Magdalena Rausch Léa Blanc Olga De Souza Silva Olivier Dormond Arjan W. Griffioen Patrycja Nowak-Sliwinska Characterization of Renal Cell Carcinoma Heterotypic 3D Co-Cultures with Immune Cell Subsets Cancers 3D co-cultures combination therapy heterotypic spheroids immune cells immunotherapy infiltration |
| title | Characterization of Renal Cell Carcinoma Heterotypic 3D Co-Cultures with Immune Cell Subsets |
| title_full | Characterization of Renal Cell Carcinoma Heterotypic 3D Co-Cultures with Immune Cell Subsets |
| title_fullStr | Characterization of Renal Cell Carcinoma Heterotypic 3D Co-Cultures with Immune Cell Subsets |
| title_full_unstemmed | Characterization of Renal Cell Carcinoma Heterotypic 3D Co-Cultures with Immune Cell Subsets |
| title_short | Characterization of Renal Cell Carcinoma Heterotypic 3D Co-Cultures with Immune Cell Subsets |
| title_sort | characterization of renal cell carcinoma heterotypic 3d co cultures with immune cell subsets |
| topic | 3D co-cultures combination therapy heterotypic spheroids immune cells immunotherapy infiltration |
| url | https://www.mdpi.com/2072-6694/13/11/2551 |
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