期刊
CANCER MEDICINE
卷 10, 期 16, 页码 5589-5598出版社
WILEY
DOI: 10.1002/cam4.4114
关键词
colorectal cancer; immune therapeutics; organotypic tumor spheroid; patient-derived cancer model; tumor microenvironment
类别
资金
- Institute of Information & Communications Technology Planning & Evaluation (IITP) [2019-0-00047]
- National Research Foundation of Korea (NRF) [2020R1F1A1075646]
- Ministry of Trade, Industry and Energy (MOTIE)
- Korea Institute for Advancement of Technology (KIAT) through the International Cooperative R&D program - Korean government (MSIT) [P0011266]
- Ministry of Health & Welfare (MOHW), Republic of Korea [P0011266] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- National Research Foundation of Korea [2020R1F1A1075646] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Patient-derived organotypic tumor spheroids (PDOTS) are a novel ex vivo system that retains key features of the native tumor immune microenvironment. The PDOTS model may represent an advantageous ex vivo system for developing effective immune therapeutics.
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.
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