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Establishment of patient-derived organotypic tumor spheroid models for tumor microenvironment modeling
Cited 14 time in
Web of Science
Cited 15 time in Scopus
- Authors
- Issue Date
- 2021-08
- Publisher
- John Wiley and Sons Ltd
- Citation
- Cancer Medicine, Vol.10 No.16, pp.5589-5598
- Abstract
- Patient-derived cancer models that reconstitute the characteristics of the tumor microenvironment may facilitate efforts in precision immune-oncology and the discovery of effective anticancer therapies. Organoids that have recently emerged as robust preclinical models typically contain tumor epithelial cells and lack the native tumor immune microenvironment. A patient-derived organotypic tumor spheroid (PDOTS) is a novel and innovative ex vivo system that retains key features of the native tumor immune microenvironment. Here, we established and characterized a series of colorectal cancer PDOTS models for use as a preclinical platform for testing effective immunotherapy and its combinations with other drugs. Partially dissociated (> 100 mu m in diameter) tumor tissues were embedded in Matrigel-containing organoid media and subsequently formed into organoid structures within 3 to 7 days of culture. The success rate of growing PDOTS from fresh tissues was similar to 86%. Morphological analysis showed that the PDOTSs varied in size and structure. Immunofluorescence and flow cytometry analysis revealed that the PDOTSs retained autologous tumor-infiltrating lymphoid cells and tumor-infiltrating lymphoid cells were continually decreased through serial passages. Notably, PDOTSs from tumors from a high-level microsatellite instability-harboring patient were sensitive to anti-PD-1 or anti-PD-L1 antibodies. Our results demonstrate that the PDOTS model in which the tumor immune microenvironment is preserved may represent an advantageous ex vivo system to develop effective immune therapeutics.
- ISSN
- 2045-7634
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