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Establishment of patient-derived organotypic tumor spheroid models for tumor microenvironment modeling

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dc.contributor.authorHong, Hye Kyung-
dc.contributor.authorYun, Nak Hyeon-
dc.contributor.authorJeong, Ye-Lin-
dc.contributor.authorPark, Jeehun-
dc.contributor.authorDoh, Junsang-
dc.contributor.authorLee, Woo Yong-
dc.contributor.authorCho, Yong Beom-
dc.date.accessioned2024-05-16T01:21:31Z-
dc.date.available2024-05-16T01:21:31Z-
dc.date.created2021-07-28-
dc.date.created2021-07-28-
dc.date.created2021-07-28-
dc.date.issued2021-08-
dc.identifier.citationCancer Medicine, Vol.10 No.16, pp.5589-5598-
dc.identifier.issn2045-7634-
dc.identifier.urihttps://hdl.handle.net/10371/202455-
dc.description.abstractPatient-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.-
dc.language영어-
dc.publisherJohn Wiley and Sons Ltd-
dc.titleEstablishment of patient-derived organotypic tumor spheroid models for tumor microenvironment modeling-
dc.typeArticle-
dc.identifier.doi10.1002/cam4.4114-
dc.citation.journaltitleCancer Medicine-
dc.identifier.wosid000670864800001-
dc.identifier.scopusid2-s2.0-85109734121-
dc.citation.endpage5598-
dc.citation.number16-
dc.citation.startpage5589-
dc.citation.volume10-
dc.description.isOpenAccessY-
dc.contributor.affiliatedAuthorDoh, Junsang-
dc.type.docTypeArticle-
dc.description.journalClass1-
dc.subject.keywordPlusORGANOID MODELS-
dc.subject.keywordPlusHUMAN COLON-
dc.subject.keywordPlusCANCER-
dc.subject.keywordPlusBLOCKADE-
dc.subject.keywordAuthorcolorectal cancer-
dc.subject.keywordAuthorimmune therapeutics-
dc.subject.keywordAuthororganotypic tumor spheroid-
dc.subject.keywordAuthorpatient-derived cancer model-
dc.subject.keywordAuthortumor microenvironment-
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  • College of Engineering
  • Department of Materials Science & Engineering
Research Area Ex Vivo Models, Lymphocyte Biology, Smart Biomaterials

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