Oncolytic Viral Therapy for Malignant Pleural Mesothelioma

Our plain-English summary of Oncolytic Viral Therapy for Malignant Pleural Mesothelioma, by H. Yang, D. Xu, Y. Gao, et al (Journal of Thoracic Oncology, 2020).

The study

• Authors: H. Yang, D. Xu, Y. Gao, R.A. Schmid, R.W. Peng
• Journal: Journal of Thoracic Oncology
• Published: 2020;15(7):e111-e113
• Type of article: Letter, Comment
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Summary of the article

In this letter to the editor, the authors commented on a study by Delaunay et al. reporting that homozygous deletions (HDs) of type I interferon (IFN-I) genes were frequent in malignant pleural mesothelioma (MPM), co-occurred with HDs of CDKN2A, and were associated with sensitivity to oncolytic measles virus (MV) therapy. The authors noted that not all MV-sensitive cell lines in that study had an HD of IFNB1 (the letter cites "eight of 15"). They also noted that three of four MV-resistant cell lines had a CDKN2A HD. They took this to mean that other mechanisms were involved. Using data on The Cancer Genome Atlas (TCGA) pleural mesothelioma cohort (n = 81) from cBioPortal, they described the frequency and overlap of alterations in CDKN2A/B, BAP1, NF2 and TP53. Of the samples with CDKN2A HDs, 46.9% had a co-occurring BAP1 alteration. They identified genes correlated with BAP1 mRNA level and performed Gene Ontology and Reactome enrichment analysis. Genes highly negatively correlated with BAP1 expression (Spearman's r < -0.4, q-value < 0.01) were significantly enriched in the IFN-I pathway, but positively correlated genes were not. The authors suggested that MPM with BAP1 loss of function might be correlated with resistance to oncolytic viral therapy, and MPM with regular or high BAP1 expression with sensitivity. They concluded that combining CDKN2A and BAP1 status might be needed to select patients, and that further studies were warranted.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

In plain English

This was a letter to the editor, not a full study. The authors were responding to an earlier study by Delaunay and colleagues. That study had linked homozygous deletions (loss of both copies) of type I interferon (IFN-I) genes in malignant pleural mesothelioma (MPM) to sensitivity to an oncolytic (cancer-killing) measles virus. The authors reanalyzed publicly available genetic data from The Cancer Genome Atlas (TCGA) pleural mesothelioma cohort of 81 samples. They reported that 46.9% of samples with homozygous deletions of the CDKN2A gene also had an alteration of the BAP1 gene. They also reported that BAP1 gene expression correlated significantly with an IFN-I signature. Genes strongly negatively correlated with BAP1 levels were enriched in the IFN-I pathway, while positively correlated genes were not. The authors wrote that this suggests MPM with loss of BAP1 function might be correlated with resistance to oncolytic viral therapy. They added that combining CDKN2A and BAP1 status might be required to select patients for such therapy. The letter did not address asbestos exposure.

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 commenting on a study by Delaunay et al., with the authors' own reanalysis of publicly available TCGA genetic and gene-expression data
• Who was studied: Tumor samples in The Cancer Genome Atlas (TCGA) pleural mesothelioma cohort, 81 samples; data downloaded from cBioPortal
• Exposure: No asbestos or other exposure was studied. The letter examined genetic alterations (BAP1, CDKN2A/B and others) in relation to possible sensitivity to oncolytic viral therapy.
• Main results:
  • In the TCGA MPM samples, 46.9% of samples with homozygous deletions of CDKN2A also had a genetic alteration of BAP1
  • In the TCGA MPM cohort, BAP1 gene expression correlated significantly with an IFN-I signature. Genes highly negatively correlated with BAP1 mRNA levels (Spearman's r below -0.4, adjusted p below 0.01) were enriched in the IFN-I pathway; genes positively correlated with BAP1 were not.
  • The authors interpreted this as suggesting that MPM with BAP1 loss of function might be correlated with resistance to oncolytic viral therapy, and MPM with regular or high BAP1 expression with sensitivity to it
• The authors' conclusion: The authors concluded that further stratification combining the genetic status of CDKN2A and BAP1 might be required to select patients with MPM for oncolytic viral therapy

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, Homozygous Deletion, CDKN2A, BAP1.

Related studies

• Reply to: Oncolytic Viral Therapy for Malignant Pleural Mesothelioma — D. Jean, T. Delaunay, 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)
• Frequent Homozygous Deletions of Type I Interferon Genes in Pleural Mesothelioma Confer Sensitivity to Oncolytic Measles Virus — T. Delaunay, C. Achard, et al. (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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