Project description:Mesothelioma is a cancer derived from mesothelial cells, most commonly arising from the pleura or the peritoneum. Immune checkpoint therapy (ICT) has shown survival benefit for pleural mesothelioma, but little is known about the response in peritoneal mesothelioma. Most preclinical mesothelioma models involve subcutaneous cancer cell implantation, which lacks the relevant tumour microenvironment of peritoneal mesothelioma and does not resemble the clinical presentation. We therefore set out to explore the influence of location on the mesothelioma tumour microenvironment, comparing pleural, peritoneal, and subcutaneous models using identical cell line-derived syngeneic mesotheliomas. We found that the peritoneal location conferred an anti-inflammatory tumour microenvironment, characterised by low IFN, TNFα, and STAT signalling activity, low immune cell infiltration and a gene signature associated with non-response to ICT. ICT was effective in subcutaneous models, but the same cell line-derived tumours were irresponsive when inoculated intraperitoneally. Together, these findings show that peritoneal location is associated with an immune suppressive tumour microenvironment.

2025-11-25 | GSE310501 | GEO

HLA-DRB1*07:01 is associated with a higher risk of asparaginase allergies.

Project description: Not available

| S-EPMC4141516 | biostudies-literature

Gene expression profiles in MexTAg transgenic mouse and wild type mouse asbestos-induced mesothelioma

Project description:Malignant mesothelioma is an aggressive tumour arising from the mesothelial cells lining the pleura, peritoneum or pericardium. The principal carcinogen associated with malignant mesothelioma is asbestos . A transgenic mouse model, denoted MexTAg, which encodes the Simian Virus 40 (SV40) large T antigen (TAg) downstream of the mesothelin promoter was developed. Inactivation of the tumour suppressors p53 and RB following binding to TAg results. In this model mesothelioma develops in the mesothelial cell compartment after the mice have been exposed to asbestos. The MexTAg transgenic mouse model of mesothelioma model enables analysis of the molecular events associated with asbestos induced mesothelioma and is utilised here to investigate the molecular dynamics of tumours induced in these mice, using gene expression patterns as a read out.

2016-01-30 | E-MTAB-3988 | biostudies-arrayexpress

Gene expression changes between primary mesothelioma tumour cells and commercially available cell lines, compared to normal primary mesothelial cells

Project description:Malignant mesothelioma (MM) is an aggressive, fatal tumour strongly associated with asbestos exposure. There is an urgent need to improve MM patient outcomes and this requires functionally validated pre-clinical models. Mesothelioma-derived cell lines provide an essential and robust tool widely used for candidate drug evaluation. Although a number of cell lines are commercially available, a detailed comparison of these lines with freshly-derived primary tumour cells to validate their suitability as pre-clinical models is lacking. Patient-derived primary mesothelioma cell lines were established and characterised by gene expression profiling. Molecular profiling revealed a significantly different transcriptome in commercially available compared with primary cell lines. Primary mesothelioma cell lines are more representative of the tumour close to its native state and show a degree of molecular diversity, thus capturing the disease heterogeneity in a patient cohort.

2018-02-01 | E-MTAB-6351 | biostudies-arrayexpress

Two tagging single-nucleotide polymorphisms to capture HLA-DRB1*07:01-DQA1*02:01-DQB1*02:02 haplotype associated with asparaginase hypersensitivity.

Project description: Not available

| S-EPMC8247313 | biostudies-literature