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

Our plain-English summary of Patient-derived malignant pleural mesothelioma cell cultures: a tool to advance biomarker-driven treatments, by N.I. Kanellakis, R. Asciak, M.A. Hamid, et al (Thorax, 2020).

The study

• Authors: N.I. Kanellakis, R. Asciak, M.A. Hamid, X. Yao, M. McCole, S. McGowan, E. Seraia, S. Hatch, R.J. Hallifax, R.M. Mercer, E.O. Bedawi, S. Jones, C. Verrill, M. Dobson, V. George, G.T. Stathopoulos, Y. Peng, D. Ebner, T. Dong, N.M. Rahman, I. Psallidas
• Journal: Thorax
• Published: 2020;75(11):1004-1008
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

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.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

In plain English

This brief communication described a laboratory study testing whether cells grown from patients could serve as a model of malignant pleural mesothelioma. It does not report on asbestos exposure. The authors grew 16 cell cultures from malignant pleural effusion samples. A pathologist confirmed the cells were malignant, and the cultures formed tumour spheres, which the authors took to indicate a tumour stem cell subpopulation. Genome sequencing of three cultures showed varied mutations in six mesothelioma-related genes. Tested against 316 FDA-approved anticancer drugs, the three cultures responded differently, and six drugs were consistently more toxic to the cells than pemetrexed/cisplatin, the current first-line chemotherapy. The culture most sensitive to pemetrexed/cisplatin came from a patient who responded to chemotherapy. Two biphasic cultures triggered cancer-specific T cell responses without added SSX-2 peptide. They also had statistically significantly higher SSX2 gene expression than two epithelioid cultures. The authors concluded the cultures suggest a faithful model of the disease. They noted that only 45% of attempts produced a culture and that the drug findings need further validation.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory feasibility study (brief communication) establishing and characterising patient-derived cancer cell cultures as an ex vivo model
• Who was studied: 16 malignant pleural mesothelioma cell cultures grown from malignant pleural effusion specimens. The number of patients is not stated in the main text, and some cultures came from the same patient at different timepoints. Subsets were studied further: three by genome sequencing and drug screening, and four (two epithelioid, two biphasic) in T cell coculture.
• Exposure: Not studied. The article does not report asbestos or any other exposure of the patients. In the laboratory, the cells were exposed to 316 FDA-approved antitumour drugs and to SSX2-specific cytotoxic CD8+ T cells.
• Main results:
  • A consultant pathologist examined stained specimens of the cultures and confirmed they were malignant.
  • The cultures formed tumour spheroids, which the authors interpreted as indicating a tumour stem cell subpopulation.
  • Whole-genome sequencing of three cultures showed varied mutation profiles in the genes TRP53, NF2, BAP1, LATS2, SETD2 and CDKN2A.
  • In drug screening of the three sequenced cultures, six drugs (bortezomib, carfilzomib, dactinomycin, dinaciclib, omacetaxine and idarubicin) were consistently more cytotoxic than pemetrexed/cisplatin.
  • Culture MESO-163 was the most sensitive to pemetrexed/cisplatin. Patient MESO-163 responded to chemotherapy, while patient MESO-031, whose culture was less sensitive, did not.
  • Two biphasic cultures (MESO-174, MESO-392) induced cytotoxic T cell responses without SSX2 peptide loading. They had statistically significantly higher SSX2 gene expression than the epithelioid cultures MESO-044 and MESO-278.
• The authors' conclusion: The authors concluded that patient-derived MPM cell cultures closely resemble the clinical phenotype and features of MPM, suggesting a faithful ex vivo human model.
• Limitations the authors state:
  • Establishing a cell culture takes a relatively long time (1 to 2 months).
  • The success rate of culture establishment (45%) needs improvement, and the reasons some samples fail need investigation.
  • The drug screening hits need validation with experiments that directly measure cell death.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Biomarker, Prognosis, Biphasic Mesothelioma.

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