Malignant pleural mesothelioma (MPM) is an aggressive cancer, associated with poor prognosis. We assessed the feasibility of patient-derived cell cultures to serve as an ex vivo model of MPM. Patient-derived MPM cell cultures (n=16) exhibited stemness features and reflected intratumour and interpatient heterogeneity. A subset of the cells were subjected to high-throughput drug screening and coculture assays with cancer-specific cytotoxic T cells and showed diverse responses. Some of the biphasic MPM cells were capable of processing and presenting the neoantigen SSX-2 endogenously. In conclusion, patient-derived MPM cell cultures are a promising and faithful ex vivo model of MPM.
Last. Marc Ladanyi(MSK: Memorial Sloan Kettering Cancer Center)H-Index: 165
view all 59 authors...
Malignant pleural mesothelioma (MPM) is a highly lethal cancer of the lining of the chest cavity. To expand our understanding of MPM, we conducted a comprehensive integrated genomic study, including the most detailed analysis of BAP1 alterations to date. We identified histology-independent molecular prognostic subsets, and defined a novel genomic subtype with TP53 and SETDB1 mutations and extensive loss of heterozygosity. We also report strong expression of the immune checkpoint gene VISTA in ep...
#1I Woolhouse(University Hospitals Birmingham NHS Foundation Trust)H-Index: 6
#1Ian Woolhouse(University Hospitals Birmingham NHS Foundation Trust)H-Index: 8
Last. Nick A Maskell(UoB: University of Bristol)H-Index: 51
view all 17 authors...
Section 3: Clinical features which predict the presence of mesothelioma Recommendations Section 4: Staging systems Recommendation Section 5: Imaging modalities for diagnosing and staging Recommendations Section 6: Pathological diagnosis Recommendations
Malignant pleural mesothelioma is an aggressive malignancy of the pleural surface, predominantly caused by prior asbestos exposure. There is a global epidemic of malignant pleural mesothelioma underway, and incidence rates are predicted to peak in the next few years. This article summarises the epidemiology and pathogenesis of malignant pleural mesothelioma, before describing some key factors in the patient experience and outlining common symptoms. Diagnostic approaches are reviewed, including i...
Asbestos is a global killer. Despite lessons learned in the developed world on the use of asbestos and its hazardous pulmonary consequences, its use continues to increase in Asia. Although some countries such as Japan, Korea and Singapore have curtailed the use of this mineral, there are numerous countries in Asia that continue to mine, import and use this fibre, particularly China, which is one of the largest consumers in the world. Numerous factors ranging from political and economic to the la...
#2Robert D. Schreiber(WashU: Washington University in St. Louis)H-Index: 119
The clinical relevance of T cells in the control of a diverse set of human cancers is now beyond doubt. However, the nature of the antigens that allow the immune system to distinguish cancer cells from noncancer cells has long remained obscure. Recent technological innovations have made it possible to dissect the immune response to patient-specific neoantigens that arise as a consequence of tumor-specific mutations, and emerging data suggest that recognition of such neoantigens is a major factor...
The incidence of mesothelioma is estimated to rise sharply worldwide, including Japan, in the next two decades. Molecular and proteomic studies are urgently required to elucidate the pathobiology of malignant mesothelioma. This paper describes the characterization of novel human malignant pleural mesothelioma cell lines representing the sarcomatoid, epithelioid and biphasic subtypes. Materials and Methods: Established pleural effusion fluid cell lines were observed using phase-contrast microscop...
The contribution of tumorigenic stem cells to haematopoietic cancers has been established for some time, and cells possessing stem-cell properties have been described in several solid tumours. Although chemotherapy kills most cells in a tumour, it is believed to leave tumour stem cells behind, which might be an important mechanism of resistance. For example, the ATP-binding cassette (ABC) drug transporters have been shown to protect cancer stem cells from chemotherapeutic agents. Gaining a bette...
: Malignant mesothelioma is an aggressive and rare tumor of the mesothelium which arises in serosal cavities and is strongly related to asbestos exposure. The incidence of this tumor is still increasing because of the widespread use of asbestos over the past years and the long latency of this malignancy. The paucity of well-characterized in vitro human models and the consequent shortage of experimental pharmacological studies on mesothelioma reduce the success of its clinical management. It is w...
Malignant mesothelioma (MM) is an aggressive tumour of the serosal cavities which is associated with exposure to asbestos. Studies of this tumour have been limited by a paucity of well-characterized human MM cell lines. In this study, 5 human MM cell lines were established from pleural effusions of patients with this malignancy. All 5 patients were males with known crocidolite asbestos exposure, who had received no treatment for their disease and in whom the diagnosis was confirmed by cytology, ...
Seventeen human malignant mesothelioma cell lines were isolated from 61 samples (46 effusions, 9 biopsies and 6 tumors obtained at autopsy) collected from patients with a confirmed malignant mesothelioma. The method used is given in detail. Cytogenetic analysis of growing cultures is the best indicator to determine whether the observed proliferation concerns malignant or normal mesothelial cells. The addition of epidermal growth factor (EGF) and hydrocortisone (HC), or EGF alone, to the culture ...
Objectives Patients with malignant pleural mesothelioma (MPM) or pleural metastases often present with malignant pleural effusion (MPE). This study aimed to analyze the effect of pleural fluid on cancer cells. Materials and methods Established patient-derived cancer cell cultures derived from MPE (MPM, breast carcinoma, lung adenocarcinoma) were seeded in 100% pleural fluid (exudate MPM MPE, transudate MPE, non-MPE transudate fluid) and proliferation was monitored. In addition, the establishment...
Malignant pleural mesothelioma (MPM) is an aggressive cancer most commonly caused by prior exposure to asbestos. Median survival is 12-18 months, since surgery is ineffective and chemotherapy offers minimal benefit. Preclinical models that faithfully recapitulate the genomic and histopathological features of cancer are critical for the development of new treatments. The most commonly used models of MPM are two-dimensional cell lines established from primary tumours or pleural fluid. While these ...
Background: Malignant pleural mesothelioma (MPM) is a very aggressive tumor originating from mesothelial cells. Although several etiological factors were reported to contribute to MPM onset, environmental exposure to asbestos is certainly a major risk factor. The latency between asbestos (or asbestos-like fibers) exposure and MPM onset is very long. MPM continues to be a tumor with poor prognosis despite the introduction of new therapies including immunotherapy. One of the major problems is the ...