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

Angelica Rigutto; Nicolás G Núñez; Jenny C Kienzler; Isabelle Opitz; Mayura Meerang; Martina Haberecker; Nadine Fournier; Joao Lourenço; Raphael Gottardo; Karina Silina; Anurag Gupta; Burkhard Becher; Alessandra Curioni-Fontecedro

doi:10.1038/s41416-026-03421-1

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

Br J Cancer. 2026 Apr 27. doi: 10.1038/s41416-026-03421-1. Online ahead of print.

Authors

Angelica Rigutto^{1

2}, Nicolás G Núñez^{3

4}, Jenny C Kienzler³, Isabelle Opitz⁵, Mayura Meerang⁵, Martina Haberecker⁶, Nadine Fournier⁷, Joao Lourenço⁷, Raphael Gottardo⁷, Karina Silina⁸, Anurag Gupta², Burkhard Becher³, Alessandra Curioni-Fontecedro^{9

10

11}

Affiliations

¹ Department of Medical Oncology and Hematology, University Hospital Zurich, Zurich, Switzerland.
² Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland.
³ Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
⁴ Facultad de Ciencias Químicas, Departamento de Bioquímica Clínica, Universidad Nacional de Córdoba, Córdoba, Argentina.
⁵ Department of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland.
⁶ Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland.
⁷ Translational Data Science Facility, Swiss Institute of Bioinformatics, Agora Cancer Research Center, Lausanne, Switzerland.
⁸ Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.
⁹ Department of Medical Oncology and Hematology, University Hospital Zurich, Zurich, Switzerland. alessandra.curioni-fontecedro@h-fr.ch.
¹⁰ Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland. alessandra.curioni-fontecedro@h-fr.ch.
¹¹ Department of Oncology, Cantonal Hospital Fribourg, Villar sur Glâne, Switzerland. alessandra.curioni-fontecedro@h-fr.ch.

PMID: 42045540
DOI: 10.1038/s41416-026-03421-1

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.