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Scientific article
Open access
English

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

Published inCancers, vol. 13, no. 11, 2551
Publication date2021-05-22
First online date2021-05-22
Abstract

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.

Keywords
  • 3D co-cultures
  • PD-L1
  • Combination therapy
  • Heterotypic spheroids
  • Immune cells
  • Immunotherapy
  • Infiltration
  • Renal cell carcinoma
  • Sunitinib
Citation (ISO format)
RAUSCH, Magdalena et al. Characterization of Renal Cell Carcinoma Heterotypic 3D Co-Cultures with Immune Cell Subsets. In: Cancers, 2021, vol. 13, n° 11, p. 2551. doi: 10.3390/cancers13112551
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ISSN of the journal2072-6694
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Technical informations

Creation01/20/2022 8:00:00 AM
First validation01/20/2022 8:00:00 AM
Update time03/16/2023 2:43:16 AM
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