Biomarkers to predict the benefits of immune‑checkpoint blockade‑based therapy in patients with malignant peritoneal mesothelioma (Review)

Our plain-English summary of Biomarkers to predict the benefits of immune‑checkpoint blockade‑based therapy in patients with malignant peritoneal mesothelioma (Review), by C. Wang, Y. Zhao, W. Liang (Oncology Letters, 2024).

The study

• Authors: C. Wang, Y. Zhao, W. Liang
• Journal: Oncology Letters
• Published: 2024;28(6):600
• Type of article: Review
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant peritoneal mesothelioma (MPeM) is a type of rare and highly lethal tumor. Immune checkpoint blockade (ICB)-based therapy has shown encouraging clinical activity for MPeM. However, no definitive biomarkers have been identified for predicting which patients with MPeM will benefit from ICB-based therapy. At present, there are several novel potential biomarkers proposed for predicting the response to ICB-based therapy, and biomarkers available in MPeM cells and in the tumor microenvironment have been identified with the potential to predict the efficacy of ICB-based therapy in MPeM. According to the molecular characteristics of MPeM itself, the feasibility of biomarkers in practice, and the body of available evidence, we hypothesize that the following five types of biomarkers can be used to predict the response of ICB-based therapy in patients with MPeM: Tertiary lymphoid structures, immune checkpoints and their ligands, fusion gene neoantigen burden, BRCA1-associated protein-1 haploinsufficiency and transcriptome-based biomarkers. The present review discusses the value and limitations of each type of biomarker, and potential solutions to address the limitations are proposed. The aim of the present review is to provide a background for future studies on ICB-based therapy for MPeM.

Copyright: © 2024 Wang et al.

In plain English

This article was a review, not a new study. The authors, from the Second Hospital of Jilin University in China, looked at published research on biomarkers: tumor and immune features that might show which patients with malignant peritoneal mesothelioma (MPeM, the form in the lining of the abdomen) would benefit from immune checkpoint blockade drugs. They discussed five types: tertiary lymphoid structures (clusters of immune cells in tissue), immune checkpoints and their ligands (PD-L1, VISTA and LAG-3), fusion gene neoantigen burden, BAP1 haploinsufficiency, and transcriptome-based (gene activity) markers. Their assessment was that no study had yet tested tertiary lymphoid structures as a predictor in MPeM, and that there was no solid evidence supporting PD-L1. They judged BAP1 loss alone possibly inadequate. They called for additional studies of tertiary lymphoid structures, prospective studies of fusion gene neoantigen burden and prospective trials of transcriptome-based scores. The authors concluded that a wider range of biomarkers is required, and that combining several measures is the more sensible approach. They noted that these biomarkers reflect only a small part of the tumor changes in MPeM. The review did not discuss 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: Narrative review of published studies. No literature search method is described.
• Who was studied: Published research on patients with malignant peritoneal mesothelioma (MPeM). The review also drew on evidence from malignant pleural mesothelioma, other cancers and laboratory or animal models. The number of studies reviewed is not stated.
• Exposure: Not an exposure study; asbestos is not discussed. The review concerns immune checkpoint blockade drugs and biomarkers that might predict response to them.
• Main results:
  • As background, the review cited a real-world study of MPeM patients treated second-line with nivolumab plus ipilimumab or a single checkpoint inhibitor, in which the objective response rate was 19.2% (5/26).
  • The review also cited a phase II single-center study of 20 MPeM patients treated second-line with atezolizumab plus bevacizumab, in which the objective response rate was 40% (8/20).
  • On tertiary lymphoid structures, the authors found no studies of whether these structures predict response to checkpoint blockade in MPeM.
  • The authors said additional studies are required to verify the relationship between tertiary lymphoid structures and checkpoint blockade treatment in MPeM.
  • On PD-L1, the authors judged there was no solid evidence supporting PD-L1 expression as a predictor in MPeM. They noted that a cited pembrolizumab trial (8 MPeM patients, response rate 12.5%) found PD-L1 expression not associated with response.
  • On VISTA and LAG-3, the authors proposed these, particularly combined with PD-L1, as possible biomarkers and treatment targets. This rested largely on cited laboratory studies and studies of other cancers.
  • On fusion gene neoantigen burden, the authors said it has potential as a predictor in MPeM but that prospective studies are needed to validate this.
  • On BAP1 haploinsufficiency, the authors judged that BAP1 loss alone may not be adequate to predict response, and that BAP1-based scores may be better.
  • On transcriptome-based scores (SR-score, EMS, ENLIGHT-DeepPT), the authors said these still need testing in controlled prospective clinical trials.
• The authors' conclusion: The authors concluded that a wider range of appropriate biomarkers is required to guide checkpoint blockade and other new treatments in MPeM. They also considered combining multiple measures into biomarker profiles the more sensible approach.
• Limitations the authors state:
  • The authors stated that the biomarkers discussed reflect only a small portion of the tumor changes likely to occur in MPeM.
  • The authors noted that studies of tertiary lymphoid structures in MPeM are limited.
  • The authors noted that the cited ENLIGHT-DeepPT treatment data were not yet peer-reviewed.

Topics

Medical terms in this study, explained in our Lexicon: Biomarker, Peritoneal Mesothelioma, Tumor Microenvironment.

Related studies

• Combination immune checkpoint blockade as an effective therapy for mesothelioma — V.S. Fear, C. Tilsed, et al. (2018)
• Success of Checkpoint Blockade Paves the Way for Novel Immune Therapy in Malignant Pleural Mesothelioma — L. Rondon, R. Fu, et al. (2023)
• Immune checkpoint blockade therapy of mesothelioma: a clinical and radiological challenge — L. Calabrò, A. Morra, et al. (2018)
• In-depth profiling of tumor tissue derived from malignant pleural mesothelioma patients identifies potential biomarkers predicting response to immune-checkpoint inhibitor therapy — D. Shek, B. Gao, et al. (2024)
• Cisplatin plus pemetrexed therapy and subsequent immune checkpoint inhibitor administration for malignant peritoneal mesothelioma without pleural lesions: Case report — H. Ikushima, T. Sakatani, et al. (2020)
• Matter of TIME: the tumor-immune microenvironment of mesothelioma and implications for checkpoint blockade efficacy — J. Harber, T. Kamata, et al. (2021)

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