Multiplexed single-cell and spatial profiling reveal B cells and tertiary lymphoid structures as prognostic indicators in pleural mesothelioma

Our plain-English summary of Multiplexed single-cell and spatial profiling reveal B cells and tertiary lymphoid structures as prognostic indicators in pleural mesothelioma, by A. Rigutto, N.G. Núñez, J.C. Kienzler, et al (British Journal of Cancer, 2026).

The study

• Authors: A. Rigutto, N.G. Núñez, J.C. Kienzler, I. Opitz, M. Meerang, M. Haberecker, N. Fournier, J. Lourenço, R. Gottardo, K. Silina, A. Gupta, B. Becher, A. Curioni-Fontecedro
• Journal: British Journal of Cancer
• Published: 2026;135(2):214-222
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Pleural mesothelioma (PM) is an orphan disease with poor prognosis. While T cell dynamics in the tumor microenvironment (TME) have been extensively studied, the role of B cells remains poorly characterized. Tumor-infiltrating B cells, particularly when organized into tertiary lymphoid structures (TLS), have been associated with improved outcomes of patients with cancer.

Methods: In this study, high-dimensional flow cytometry (HDCyto) and high-plex imaging were applied to analyze fresh-frozen and formalin-fixed paraffin-embedded (FFPE) PM tumor samples, enabling a comprehensive immune profiling of the TME.

Results: We identified 15 distinct immune cell subsets and stratified tumors into three subgroups with significantly different survival outcomes. Longer survival correlated with increased T and B cell infiltration, with B cells and CD4+ T cells forming TLS in specific cases.

Conclusions: These findings underscore the heterogeneity of PM tumors and highlight the critical role of B cells and TLS in shaping anti-tumor immunity and influencing patient prognosis.

© 2026. The Author(s).

In plain English

This study examined immune cells in pleural mesothelioma tumour samples from 41 patients at the University Hospital Zurich, collected from 2017 to 2021. Of the 41, 39 were men. Asbestos exposure was recorded as yes for 28, possible for 10 and no for 3, but exposure was not analysed further. Using single-cell laboratory methods, the authors identified 15 types of immune cells and sorted the tumours into three groups of 22, 12 and 7 patients. Group 3 tumours mostly contained myeloid cells, with more tumour-associated macrophages, while groups 1 and 2 had more B cells and T cells. Median overall survival was 31.9, 18.5 and 7.3 months in groups 1, 2 and 3. In 30 tumours examined by imaging, groups 1 and 2 had a significantly higher density of tertiary lymphoid structures (organised clusters of B and T cells) than group 3. The authors concluded that these structures marked tumours from patients with improved survival. They noted the small number of samples, especially in group 3, and the need for a larger study.

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: Laboratory study of tumour samples (high-dimensional spectral flow cytometry and high-plex imaging) from a patient cohort, with survival analysis
• Who was studied: 54 pleural mesothelioma patients enrolled 2017 to 2021 at the University Hospital Zurich; 13 excluded, leaving 41 analysed (39 male, 2 female; mean age 68.4 years, range 53 to 83; 37 epithelioid, 1 sarcomatoid, 3 biphasic). 30 matching FFPE tumours were used for imaging.
• Exposure: The study examined immune cells within tumours, not asbestos exposure. Asbestos exposure was recorded only as a patient characteristic: yes in 28 (68.3%), possible in 10 (24.4%), no in 3 (7.3%). No fiber types, jobs or doses were reported.
• Main results:
  • 15 immune cell subsets were identified in the tumours.
  • Tumours fell into three subgroups: group 1 had 22 samples, group 2 had 12 and group 3 had 7.
  • Groups 1 and 2 were enriched in lymphoid cells (B cells, CD4+ and CD8+ T cells), while group 3 mostly contained myeloid cells.
  • Median overall survival was 31.9 months in group 1, 18.5 months in group 2 and 7.3 months in group 3. Group 3 was significantly worse than groups 1 and 2 (p less than 0.0001).
  • Median progression-free survival was 13.7 months in group 1, 16.2 months in group 2 and 5.2 months in group 3 (p less than 0.0001 for group 3 compared with groups 1 and 2).
  • In a multivariate analysis including chemotherapy, surgery, gender and age, belonging to group 3 was the only significant prognostic factor for overall and progression-free survival.
  • B cells were more abundant in groups 1 and 2 than in group 3, highest in group 2. Group 3 had more tumour-associated macrophages (TAMs and FOLR2+ TAMs).
  • In 30 FFPE tumours (group 1 = 15, group 2 = 11, group 3 = 4), total tertiary lymphoid structure density was significantly higher in groups 1 and 2 than in group 3. Most structures were in peritumoral areas.
  • Densities of tertiary lymphoid structures at each maturation stage (early, primary follicle-like, secondary follicle-like) did not differ significantly among groups. Groups 1 and 2 had a significantly higher absolute number of early structures than group 3.
• The authors' conclusion: The authors concluded that the immune cells in pleural mesothelioma tumours fall into three subgroups. They found that tertiary lymphoid structures characterised tumours from patients with improved survival, and suggested these structures may serve as prognostic biomarkers.
• Limitations the authors state:
  • The number of patient samples was limited, especially in group 3.
  • The findings need validation in a larger cohort of mesothelioma cases.

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Prognosis, Tumor Microenvironment.

Related studies

• Tertiary lymphoid structures in epithelioid malignant peritoneal mesothelioma are associated with neoadjuvant chemotherapy, but not with prognosis — N. Benzerdjeb, P. Dartigues, et al. (2021)
• Epithelioid Pleural Mesothelioma Is Characterized by Tertiary Lymphoid Structures in Long Survivors: Results from the MATCH Study — L. Mannarino, L. Paracchini, et al. (2022)
• Anti-mesothelin immunotoxin induces mesothelioma eradication, anti-tumor immunity, and the development of tertiary lymphoid structures — W. Liu, C.H. Tai, et al. (2022)
• Comparison of imaging based single-cell resolution spatial transcriptomics profiling platforms using formalin-fixed paraffin-embedded tumor samples — N. Ozirmak Lermi, M. Molina Ayala, et al. (2025)
• Insights into Intra-Tumoral Heterogeneity: Transcriptional Profiling of Chemoresistant MPM Cell Subpopulations Reveals Involvement of NFkB and DNA Repair Pathways and Contributes a Prognostic Signature — M. Cioce, A. Sacconi, et al. (2021)
• Evaluating the effect of immune cells on the outcome of patients with mesothelioma — S.J. Chee, M. Lopez, et al. (2017)

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