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

As stated in the manuscript, 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. 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. 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  μm 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 ...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESAERCH Source Type: research