Reply to: Oncolytic Viral Therapy for Malignant Pleural Mesothelioma

Our plain-English summary of Reply to: Oncolytic Viral Therapy for Malignant Pleural Mesothelioma, by D. Jean, T. Delaunay, C. Meiller, et al (Journal of Thoracic Oncology, 2020).

The study

• Authors: D. Jean, T. Delaunay, C. Meiller, N. Boisgerault, M. Grard, S. Caruso, C. Blanquart, E. Felley-Bosco, J. Bennouna, F. Tangy, M. Grégoire, J.F. Fonteneau
• Journal: Journal of Thoracic Oncology
• Published: 2020;15(7):e113-e116
• Type of article: Letter, Comment
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

In plain English

This article is a letter to the editor in which the authors replied to a letter by Yang and colleagues. Using tumor data from The Cancer Genome Atlas, Yang and colleagues had linked low BAP1 gene expression to an active type I interferon (IFN-I) antiviral response. They suggested that BAP1 loss might mark malignant pleural mesothelioma that resists virus-based (oncolytic) therapy. The authors examined this in laboratory-grown mesothelioma cell lines. In 19 cell lines previously tested against measles virus, the virus-resistant lines had significantly lower BAP1 expression (p = 0.02). Eight of the 19 lines carried BAP1 alterations. The authors described a slight enrichment of these alterations among resistant lines (p = 0.07). All lines with deletion of the IFNB1 gene were sensitive to the virus, whatever their BAP1 status. In 36 cell lines, the authors found no significant enrichment of IFN-I pathways linked to BAP1. The authors concluded that BAP1 status may correlate with resistance to the virus but that they could not conclude a link with the IFN-I response. They suggested that the tumor microenvironment might explain the difference from tumor samples. The letter did not study asbestos.

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: Letter to the editor (reply to a previous letter) reporting laboratory analyses of mesothelioma cell lines
• Who was studied: 19 malignant pleural mesothelioma cell lines whose sensitivity to measles virus had been determined in the authors' previous study; IFN-I signature analysis in 36 short-term-cultured malignant pleural mesothelioma cell lines (61% with BAP1 alterations, 28% with IFNB1 alterations, 14% with both)
• Exposure: No asbestos exposure was studied. The factors examined were BAP1 gene expression and alteration status in relation to sensitivity to oncolytic measles virus (MV).
• Main results:
  • Among the 19 cell lines, measles-virus-resistant lines had significantly lower BAP1 expression than virus-sensitive lines (p = 0.02)
  • Eight of the 19 cell lines carried BAP1 alterations: three with homozygous deletions and five with mutations
  • All cell lines with IFNB1 deletion were sensitive to measles virus regardless of BAP1 mutation status
  • The authors described a slight enrichment of BAP1 genetic alterations in virus-resistant compared with virus-sensitive cell lines (p = 0.07 in all lines; p = 0.06 in lines without IFNB1 deletion)
  • In the 36 cell lines, no significant enrichment of IFN-I pathways was found among genes whose expression inversely correlated with BAP1 expression, or among genes differing between lines with and without BAP1 alteration (data not shown)
  • Two virus-resistant cell lines differed: Meso61 (BAP1 biallelic deletion, low BAP1 expression) had an inactivated IFN-I response, while Meso45 (high expression of wild-type BAP1) had a strong constitutively activated IFN-I response
• The authors' conclusion: The authors concluded that their results suggest a correlation between BAP1 expression or alteration status and resistance to measles virus, but that they could not conclude a link with the IFN-I response. They added that the correlation reported by Yang and colleagues could help identify patients without IFNB1 deletion who are less likely to respond to oncolytic virotherapy.
• Limitations the authors state:
  • Results differed between tumor samples and cell lines. The authors suggested this may be due to the tumor microenvironment, such as infiltrating immune cells, which cell lines lack.

Topics

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

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

Related studies

• Frequent Homozygous Deletions of Type I Interferon Genes in Pleural Mesothelioma Confer Sensitivity to Oncolytic Measles Virus — T. Delaunay, C. Achard, et al. (2020)
• Oncolytic Viral Therapy for Malignant Pleural Mesothelioma — H. Yang, D. Xu, et al. (2020)
• Personalized Oncolytic Therapy: The Next Step Toward the Successful Clinical Application of Vaccine-Strain Measles Viruses for Cancer Therapy? — T. Peikert (2020)
• Antitumor-specific T-cell responses induced by oncolytic adenovirus ONCOS-102 (AdV5/3-D24-GM-CSF) in peritoneal mesothelioma mouse model — L. Kuryk, A.W. Møller, et al. (2018)
• Enhanced antitumor efficacy of fiber-modified, midkine promoter-regulated oncolytic adenovirus in human malignant mesothelioma — M. Takagi-Kimura, T. Yamano, et al. (2013)
• BioKnife, a uPA activity-dependent oncolytic Sendai virus, eliminates pleural spread of malignant mesothelioma via simultaneous stimulation of uPA expression — Y. Morodomi, T. Yano, et al. (2012)

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