LAG3 is an independent prognostic biomarker and potential target for immune checkpoint inhibitors in malignant pleural mesothelioma - a retrospective study

Sep 24, 2026

Lymphocyte-activation gene 3 (LAG3) is an immune checkpoint receptor, and LAG3-targeting immune checkpoint inhibitors show therapeutic activity in melanoma; however, LAG3’s role in malignant pleural mesothelioma (MPM) and related LAG3 immune checkpoint inhibitors remains unclear. This retrospective study evaluated LAG3 mRNA and immunohistochemical (IHC) expression, its prognostic impact across cancers, and its potential as an immune checkpoint inhibitor target in MPM.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages11

Reading Time28 min

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Abstract

Background

Methods

Results

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Keywords

Background

Arimura etal. BMC Cancer (2023) 23:1206 [https://doi.org/10.1186/s12885-023-11636-1](https://doi.org/10.1186/s12885-023-11636-1) BMC Cancer RESEARCH Open Access LAG3 is an independent prognostic biomarker and potential target for immune checkpoint inhibitors in malignant pleural mesothelioma: a retrospective study Ken Arimura1*, Kenzo Hiroshima2†, Yoji Nagashima3, Tadao Nakazawa2, Akira Ogihara4, Mami Orimo1, Yasuto Sato5, Hideki Katsura 1, Masato Kanzaki4, Mitsuko Kondo1† and EtsukoTagaya1 Abstract Background Lymphocyte-activation gene 3 (LAG3) is an immune checkpoint receptor; novel LAG3 immune checkpoint inhibitors (ICIs) exhibit therapeutic activity in melanoma. The role of LAG3and ICIs of LAG3 are unknown in malignant pleural mesothelioma (MPM) . This study aimed to uncover the prognostic landscape of LAG3 in multiple cancers and investigate the potential of using LAG3 as an ICIs target in patients with MPM. Methods We used The Cancer Genome Atlas (TCGA) cohort for assessing mRNA expression and our cohort for immunohistochemical expression. TCGA cohort were analyzed using the Wilcoxon rank-sum test to compare mRNA expression between normal and tumor tissues in multiple cancers. We used 86 MPM cases from TCGA and 38 MPM cases from our cohort to analyze the expression of LAG3 in tumor-infiltrating lymphocytes. The mean LAG3 mRNA expression was set as the cut-off and samples were classified as positive/negative for immunohistochemical expression. Overall survival (OS) of patients with MPM was determined using the Kaplan–Meier method based on LAG3 mRNA and immunohistochemical expression. OS analysis was performed using the multivariate Cox proportional hazards model. The correlation of LAG3 expression and mRNA expression of tumor immune infiltration cells (TIICs) gene markers were estimated using Spearman correlation. To identify factors affecting the correlation of LAG3 mRNA expression, a multivariate linear regression model was performed. Results LAG3 mRNA was associated with prognosis in multiple cancers. Elevated LAG3 mRNA expression was correlated with a better prognosis in MPM. LAG3 expression was detected immunohistochemically in the membrane of infiltrating lymphocytes in MPM. LAG3 immunohistochemical expression was correlated with a better prognosis in MPM. The multivariate Cox proportional hazards model revealed that elevated LAG3 immunohistochemical expression indicated a better prognosis. In addition, LAG3 mRNA expression was correlated with the expression of various gene markers ofTIICs, the most relevant to programmed cell death 1 (PD-1) with the multivariate linear regression model in MPM. †Kenzo Hiroshima and Mitsuko Kondo contributed equally to this work and share the first authorship. *Correspondence: Ken Arimura [arimura.ken@twmu.ac.jp](arimura.ken@twmu.ac.jp) Full list of author information is available at the end of the article © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ()[. The Creative Commons Public Domain Dedication waiver (](http://creativecommons.org/licenses/by/4

FAQs

What was the study’s main objective regarding LAG3 in MPM?

To clarify the prognostic landscape of LAG3 and assess LAG3 as a potential immune checkpoint inhibitor target in patients with malignant pleural mesothelioma.

How were LAG3 levels measured in the study?

LAG3 mRNA expression was assessed using the TCGA cohort, and LAG3 protein expression was evaluated by immunohistochemistry in an MPM cohort, including samples from TCGA and the authors’ cohort.

What relationship did the study find between LAG3 expression and prognosis in MPM?

Higher LAG3 mRNA and higher LAG3 IHC expression in infiltrating lymphocytes were associated with a better prognosis, and the multivariate Cox model supported LAG3 as an independent prognostic biomarker in MPM.

Sep 24, 2026

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