Patient-derived malignant pleural mesothelioma cell cultures: a tool to advance biomarker-driven treatments

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.

[1]  A. McMichael,et al.  Enriched HLA-E and CD94/NKG2A Interaction Limits Antitumor CD8+ Tumor-Infiltrating T Lymphocyte Responses , 2019, Cancer Immunology Research.

[2]  David L. Gibbs,et al.  Integrative Molecular Characterization of Malignant Pleural Mesothelioma. , 2018, Cancer discovery.

[3]  M. Slade,et al.  British Thoracic Society Guideline for the investigation and management of malignant pleural mesothelioma , 2018, Thorax.

[4]  Nick A Maskell,et al.  Malignant pleural mesothelioma: an update on investigation, diagnosis and treatment , 2016, European Respiratory Review.

[5]  Marc Bickle,et al.  Screening out irrelevant cell-based models of disease , 2016, Nature Reviews Drug Discovery.

[6]  Ricardo Villamarín-Salomón,et al.  ClinVar: public archive of interpretations of clinically relevant variants , 2015, Nucleic Acids Res..

[7]  Donavan T. Cheng,et al.  Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT): A Hybridization Capture-Based Next-Generation Sequencing Clinical Assay for Solid Tumor Molecular Oncology. , 2015, The Journal of molecular diagnostics : JMD.

[8]  Laurie Kazan-Allen,et al.  Asbestos in Asia , 2015, Respirology.

[9]  R. Gibbs,et al.  Comparison and integration of deleteriousness prediction methods for nonsynonymous SNVs in whole exome sequencing studies. , 2015, Human molecular genetics.

[10]  T. Schumacher,et al.  Neoantigens in cancer immunotherapy , 2015, Science.

[11]  David E Larson,et al.  Using VarScan 2 for Germline Variant Calling and Somatic Mutation Detection , 2013, Current protocols in bioinformatics.

[12]  Stephen Taylor,et al.  MIG: Multi-Image Genome viewer , 2013, Bioinform..

[13]  Mauricio O. Carneiro,et al.  From FastQ Data to High‐Confidence Variant Calls: The Genome Analysis Toolkit Best Practices Pipeline , 2013, Current protocols in bioinformatics.

[14]  Pang-Kuo Lo,et al.  In vitro Tumorsphere Formation Assays. , 2013, Bio-protocol.

[15]  Mark Bernstein,et al.  Glioma stem cell lines expanded in adherent culture have tumor-specific phenotypes and are suitable for chemical and genetic screens. , 2009, Cell stem cell.

[16]  Thomas D. Schmittgen,et al.  Analyzing real-time PCR data by the comparative CT method , 2008, Nature Protocols.

[17]  Michael Dean,et al.  Tumour stem cells and drug resistance , 2005, Nature Reviews Cancer.

[18]  R. Favoni,et al.  Establishment and preliminary characterization of human malignant mesothelioma cell lines. , 1998, Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace.

[19]  A. Musk,et al.  Establishment and characterization of five human malignant mesothelioma cell lines derived from pleural effusions , 1991, International journal of cancer.

[20]  H. Hoogsteden,et al.  Establishment of human malignant mesothelioma cell lines , 1989, International journal of cancer.

[21]  Y. Ohtsuki,et al.  Establishment of three novel human malignant pleural mesothelioma cell lines: morphological and cytogenetical studies and EGFR mutation status. , 2008, Anticancer research.