BAP1 Loss Might Be a Predictive Biomarker for Immunotherapy Response in Pleural Mesothelioma

Our plain-English summary of BAP1 Loss Might Be a Predictive Biomarker for Immunotherapy Response in Pleural Mesothelioma, by R. Imase, R. Sakakibara, S. Kirimura, et al (Thoracic Cancer, 2026).

The study

• Authors: R. Imase, R. Sakakibara, S. Kirimura, H. Ishibashi, K. Okubo, Y. Miyazaki
• Journal: Thoracic Cancer
• Published: 2026;17(13):e70343
• Read it: PubMed · Publisher · Free full text

Abstract

Introduction: Reliable predictive biomarkers for immune checkpoint inhibitors (ICIs) in pleural mesothelioma (PM) are lacking. Loss of BRCA1-associated protein 1 (BAP1) is a frequent molecular alteration in PM and may influence the tumor immune microenvironment. We evaluated whether BAP1 loss is associated with clinical outcomes following immunotherapy.

Methods: We retrospectively analyzed 14 patients with PM who were treated with ICIs between April 2014 and May 2024. BAP1 status was assessed by immunohistochemical staining of resected tumor specimens. Patients were categorized into BAP1-loss and BAP1-positive groups. Progression-free survival (PFS), overall survival (OS), response rate (RR), and disease control rate (DCR) were compared.

Results: BAP1 loss was observed in nine patients (64%). Median PFS was significantly longer in the BAP1-loss group compared with the BAP1-positive group (5.3 vs. 2.1 months; log-rank p = 0.03). Median OS was also prolonged in the BAP1-loss group (8.6 vs. 2.1 months; log-rank p = 0.03). RR and DCR were numerically higher among patients with BAP1 loss.

Conclusion: BAP1 loss was associated with improved clinical outcomes following immunotherapy in PM. These findings support that a molecular profile that includes BAP1 deletion may serve as a biomarker for predicting response to immunotherapy in PM.

© 2026 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.

In plain English

This retrospective study by researchers in Tokyo, Japan, looked at 14 patients with pleural mesothelioma who were treated with immune checkpoint inhibitors: nivolumab alone, or nivolumab plus ipilimumab. Tumor samples were stained to see whether the tumor cells had lost a protein called BAP1. Nine of the 14 patients (64%) had BAP1 loss. Median progression-free survival was 5.3 months in the BAP1-loss group versus 2.1 months in the BAP1-positive group (p = 0.03). Median overall survival was 8.6 versus 2.1 months (p = 0.03). Response rate and disease control rate were numerically higher with BAP1 loss, but these differences were not statistically significant. A history of asbestos exposure was recorded for 10 of the 14 patients; fiber types were not reported. The authors concluded that BAP1 loss was associated with better outcomes after immunotherapy and called the findings preliminary. As limitations, they cited the small retrospective sample, possible selection bias, the chance that BAP1-loss patients simply had a better outlook anyway, prior chemotherapy, and reliance on staining alone.

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: retrospective observational cohort study (single institution)
• Who was studied: 14 patients with pleural mesothelioma treated with immune checkpoint inhibitors. The methods describe them as consecutive patients diagnosed between April 2014 and May 2024 who received immunotherapy on or after October 2018. 13 were male and 1 female. 9 further patients were excluded because tissue samples were insufficient. Ethics approval came from the Institute of Science Tokyo.
• Exposure: Immune checkpoint inhibitor therapy: nivolumab monotherapy (7 patients) or ipilimumab plus nivolumab (7 patients). Outcomes were compared by tumor BAP1 status, assessed by immunohistochemistry. History of asbestos exposure was recorded as a baseline characteristic; no fiber types or doses were given.
• Main results:
  • BAP1 loss was found in 9 of the 14 patients (64%).
  • Median progression-free survival was 5.3 months in the BAP1-loss group vs. 2.1 months in the BAP1-positive group (log-rank p = 0.03).
  • Median overall survival was 8.6 months in the BAP1-loss group vs. 2.1 months in the BAP1-positive group (log-rank p = 0.03).
  • Response rate and disease control rate were numerically higher in the BAP1-loss group, but the differences were not statistically significant.
  • Among patients given nivolumab monotherapy, median progression-free survival was 2.8 months in the BAP1-loss group (n = 5) vs. 2.3 months in the BAP1-positive group (n = 2) (p = 0.29). Median overall survival was 12.1 vs. 2.3 months (p = 0.008).
  • History of asbestos exposure was recorded in 10 of 14 patients overall (71%): 8 of 9 in the BAP1-loss group (89%) and 2 of 5 in the BAP1-positive group (40%), p = 0.09.
• The authors' conclusion: The authors concluded that BAP1 loss was associated with improved clinical outcomes after immunotherapy in pleural mesothelioma. They described the findings as preliminary and said that a molecular profile including BAP1 deletion may serve as a biomarker for predicting immunotherapy response, with prospective validation in larger cohorts warranted.
• Limitations the authors state:
  • The retrospective design introduces potential selection bias.
  • The sample was small, and the exclusion of many patients (9 excluded for insufficient tissue) may have caused selection bias. Validation in a larger cohort is needed.
  • The better outcomes in the BAP1-loss group might reflect an inherently better prognosis, which could not be checked in patients who did not receive immunotherapy. The authors said they cannot definitively conclude that BAP1 loss predicts immunotherapy efficacy.
  • The effects of prior chemotherapy, which all patients had received, were not considered and may have altered the tumor microenvironment.
  • BAP1 status was assessed by immunohistochemistry alone and may differ from genetic analysis.
  • Immune cell infiltration and other features of the tumor microenvironment were not directly analyzed.

Topics

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

Medical terms in this study, explained in our Lexicon: BAP1, Biomarker, Immunotherapy, Pleural Mesothelioma, checkpoint inhibitors, Immunohistochemistry, Progression-Free Survival, Overall Survival.

Related studies

• Loss of BAP1 as a candidate predictive biomarker for immunotherapy of mesothelioma — M. Ladanyi, F. Sanchez Vega, et al. (2019)
• PD-L1 and BAP1 as Prognostic Biomarkers in Malignant Pleural Mesothelioma — M. Gajić, V. Ćeriman Krstić, et al. (2026)
• Loss of BRCA1-associated protein 1 (BAP1) expression is rare in non-small cell lung cancer — D. Owen, B.S. Sheffield, et al. (2017)
• Loss of BAP1 Expression in Atypical Mesothelial Proliferations Helps to Predict Malignant Mesothelioma — R. Pillappa, J.J. Maleszewski, et al. (2018)
• Retrospective response analysis of BAP1 expression to predict the clinical activity of systemic cytotoxic chemotherapy in mesothelioma — N. Kumar, D. Alrifai, et al. (2019)
• Loss of expression of BAP1 predicts longer survival in mesothelioma — M. Farzin, C.W. Toon, et al. (2015)

Browse more research in Thoracic Cancer, or return to medical research.