Loss of BAP1 as a candidate predictive biomarker for immunotherapy of mesothelioma

Our plain-English summary of Loss of BAP1 as a candidate predictive biomarker for immunotherapy of mesothelioma, by M. Ladanyi, F. Sanchez Vega, M. Zauderer (Genome Medicine, 2019).

The study

• Authors: M. Ladanyi, F. Sanchez Vega, M. Zauderer
• Journal: Genome Medicine
• Published: 2019;11(1):18
• Type of article: Comment
• Cited by: 52 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

As trials of immune checkpoint inhibitor (ICI) therapies demonstrate responses in only a minority of pleural mesotheliomas (PlMs) and largely exclude patients with the related peritoneal mesothelioma (PeM), clinicians need predictive biomarkers of response and inclusion of PeM patients in future trials. A new study finds that loss of the deubiquitinase BAP1 in PeM correlates with an inflammatory tumor microenvironment, suggesting that BAP1 status might identify PeM, and possibly PlM, patients who would benefit from ICI therapy.

In plain English

This article is a short research highlight, a commentary, not a full original study. It discussed a separate study by Shrestha and colleagues, who analyzed 19 cases of peritoneal mesothelioma (PeM). As this article describes it, that study reported that loss of a gene called BAP1 was associated with a more inflamed tumor microenvironment. That finding belongs to Shrestha and colleagues, not to this article. The authors of the highlight also re-analyzed existing data on 74 pleural mesothelioma (PlM) samples from the TCGA cohort, grouped by BAP1 status. They found a trend, described as sub-significant, for PD-L1 to be higher in BAP1-altered samples. The most significant association they found was a stronger activated dendritic cell signature in the BAP1-altered group. Asbestos exposure was not studied. The authors concluded that examining BAP1 status in relation to immunotherapy response in mesothelioma is warranted. They cautioned that a neighboring gene, PBRM1, might be a confounding factor. They also said the 19-case findings need confirmation in larger, independent cohorts and need correlation with data on patients' responses to immunotherapy.

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: Research highlight (commentary) on a published study by Shrestha and colleagues, including the authors' own brief re-analysis of existing tumor data
• Who was studied: The authors' own re-analysis used 74 pleural mesothelioma (PlM) samples from the TCGA cohort. The study they commented on (Shrestha and colleagues) analyzed 19 peritoneal mesothelioma (PeM) cases. No locations or dates are given.
• Exposure: Not an asbestos exposure study. The factor examined was BAP1 inactivation status (BAP1-altered vs BAP1-intact tumors). No fiber types, products, jobs or doses were studied.
• Main results:
  • Reported from the Shrestha and colleagues study, not this article's own data: BAP1 loss in peritoneal mesothelioma was associated with a more inflamed tumor microenvironment, and the investigators proposed this as a possible predictor of response to immune checkpoint inhibitors
  • In the authors' re-analysis of 74 pleural mesothelioma samples, PD-L1 (CD274) showed a similar but sub-significant trend to be higher in BAP1-altered samples (p values are in Fig. 1, which is not in the text provided)
  • In the same re-analysis of pleural mesothelioma samples, the most significant association was a more prominent mRNA signature of activated dendritic cells in the BAP1-altered group
• The authors' conclusion: The authors concluded that, based on the Shrestha and colleagues data, examination of BAP1 status in relation to immunotherapy response in mesothelioma is warranted
• Limitations the authors state:
  • BAP1 lies close to PBRM1 on the same chromosome region, and the two are frequently inactivated together in PeM. The authors said this might be a confounding factor, because PBRM1 loss has been linked to immune effects in other cancers.
  • The findings from the integrated analysis of 19 PeM samples need confirmation in larger, independent cohorts
  • Clinical validation will require correlation with data on immune checkpoint inhibitor responses in relevant patient cohorts

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: BAP1, Biomarker, Immunotherapy, Mesothelioma, checkpoint inhibitors, Pleural Mesothelioma, Peritoneal Mesothelioma, Tumor Microenvironment.

Related studies

• BAP1 Loss Might Be a Predictive Biomarker for Immunotherapy Response in Pleural Mesothelioma — R. Imase, R. Sakakibara, et al. (2026)
• Immunotherapy with immune checkpoint inhibitors and predictive biomarkers in malignant mesothelioma: Work still in progress — M. Perrino, F. De Vincenzo, et al. (2023)
• BAP1 Deficiency Inflames the Tumor Immune Microenvironment and Is a Candidate Biomarker for Immunotherapy Response in Malignant Pleural Mesothelioma — D. Xu, Y. Gao, et al. (2024)
• Exploring the Expression of the «Dark Matter» of the Genome in Mesothelioma for Potentially Predictive Biomarkers for Prognosis and Immunotherapy — E. Felley-Bosco (2023)
• BAP1 haploinsufficiency predicts a distinct immunogenic class of malignant peritoneal mesothelioma — R. Shrestha, N. Nabavi, et al. (2019)
• Novel LRRK2 mutations and other rare, non-BAP1-related candidate tumor predisposition gene variants in high-risk cancer families with mesothelioma and other tumors — M. Cheung, Y. Kadariya, et al. (2021)

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