{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["67(10)"],"submitter":["Zhao Y"],"funding":["Agency for Science, Technology and Research","National Research Foundation Singapore","National Medical Research Council"],"pubmed_abstract":["<h4>Objective</h4>As the current therapeutic strategies for human hepatocellular carcinoma (HCC) have been proven to have limited effectiveness, immunotherapy becomes a compelling way to tackle the disease. We aim to provide humanised mouse (humice) models for the understanding of the interaction between human cancer and immune system, particularly for human-specific drug testing.<h4>Design</h4>Patient-derived xenograft tumours are established with type I human leucocyte antigen matched human immune system in NOD-<i>scid Il2rg<sup>-/-</sup></i> (NSG) mice. The longitudinal changes of the tumour and immune responses as well as the efficacy of immune checkpoint inhibitors are investigated.<h4>Results</h4>Similar to the clinical outcomes, the human immune system in our model is educated by the tumour and exhibits exhaustion phenotypes such as a significant declination of leucocyte numbers, upregulation of exhaustion markers and decreased the production of human proinflammatory cytokines. Notably, cytotoxic immune cells decreased more rapidly compared with other cell types. Tumour infiltrated T cells have much higher expression of exhaustion markers and lower cytokine production compared with peripheral T cells. In addition, tumour-associated macrophages and myeloid-derived suppressor cells are found to be highly enriched in the tumour microenvironment. Interestingly, the tumour also changes gene expression profiles in response to immune responses by upregulating immune checkpoint ligands. Most importantly, in contrast to the NSG model, our model demonstrates both therapeutic and side effects of immune checkpoint inhibitors pembrolizumab and ipilimumab.<h4>Conclusions</h4>Our work provides a model for immune-oncology study and a useful parallel-to-human platform for anti-HCC drug testing, especially immunotherapy."],"journal":["Gut"],"pagination":["1845-1854"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6145285"],"repository":["biostudies-literature"],"pubmed_title":["Development of a new patient-derived xenograft humanised mouse model to study human-specific tumour microenvironment and immunotherapy."],"pmcid":["PMC6145285"],"pubmed_authors":["Yang H","Toh TB","Chow PK","Chen Q","Fan Y","Liu M","Tan SY","Loh E","Chee CE","Chan XY","Lyer SG","Toh HC","Zhao Y","Tan TC","Lim SG","Chan JKY","Bonney GK","Shuen TWH","Chow EK","Zhai W","Lee GH","Dan YY","Chang KTE"],"additional_accession":[]},"is_claimable":false,"name":"Development of a new patient-derived xenograft humanised mouse model to study human-specific tumour microenvironment and immunotherapy.","description":"<h4>Objective</h4>As the current therapeutic strategies for human hepatocellular carcinoma (HCC) have been proven to have limited effectiveness, immunotherapy becomes a compelling way to tackle the disease. We aim to provide humanised mouse (humice) models for the understanding of the interaction between human cancer and immune system, particularly for human-specific drug testing.<h4>Design</h4>Patient-derived xenograft tumours are established with type I human leucocyte antigen matched human immune system in NOD-<i>scid Il2rg<sup>-/-</sup></i> (NSG) mice. The longitudinal changes of the tumour and immune responses as well as the efficacy of immune checkpoint inhibitors are investigated.<h4>Results</h4>Similar to the clinical outcomes, the human immune system in our model is educated by the tumour and exhibits exhaustion phenotypes such as a significant declination of leucocyte numbers, upregulation of exhaustion markers and decreased the production of human proinflammatory cytokines. Notably, cytotoxic immune cells decreased more rapidly compared with other cell types. Tumour infiltrated T cells have much higher expression of exhaustion markers and lower cytokine production compared with peripheral T cells. In addition, tumour-associated macrophages and myeloid-derived suppressor cells are found to be highly enriched in the tumour microenvironment. Interestingly, the tumour also changes gene expression profiles in response to immune responses by upregulating immune checkpoint ligands. Most importantly, in contrast to the NSG model, our model demonstrates both therapeutic and side effects of immune checkpoint inhibitors pembrolizumab and ipilimumab.<h4>Conclusions</h4>Our work provides a model for immune-oncology study and a useful parallel-to-human platform for anti-HCC drug testing, especially immunotherapy.","dates":{"release":"2018-01-01T00:00:00Z","publication":"2018 Oct","modification":"2026-06-17T07:02:19.457Z","creation":"2026-06-17T03:09:56.109Z"},"accession":"S-EPMC6145285","cross_references":{"pubmed":["29602780"],"doi":["10.1136/gutjnl-2017-315201"]}}