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Orthotopic Implantation and Peripheral Immune Cell Monitoring in the II-45 Syngeneic Rat Mesothelioma Model
Published on: October 2, 2015
Multiplexed single-cell and spatial profiling reveal B cells and tertiary lymphoid structures as prognostic
Angelica Rigutto1,2, Nicolás G Núñez3,4, Jenny C Kienzler3
1Department of Medical Oncology and Hematology, University Hospital Zurich, Zurich, Switzerland.
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.
Insights
Pleural mesothelioma (PM) tumors show significant immune cell heterogeneity. Increased B cell and T cell infiltration, especially within tertiary lymphoid structures (TLS), correlates with improved patient survival.
Area of Science:
- Immunology
- Oncology
- Cancer Research
Background:
- Pleural mesothelioma (PM) is an orphan disease with a poor prognosis.
- The role of B cells in the tumor microenvironment (TME) of PM is not well understood.
- Tertiary lymphoid structures (TLS) composed of B cells are linked to better outcomes in other cancers.
Purpose of the Study:
- To comprehensively profile the immune landscape of the PM tumor microenvironment.
- To investigate the prognostic significance of immune cell infiltration, particularly B cells and TLS.
- To understand the heterogeneity of immune responses in pleural mesothelioma.
Main Methods:
- Utilized high-dimensional flow cytometry (HDCyto) and high-plex imaging.
- Analyzed fresh-frozen and formalin-fixed paraffin-embedded (FFPE) PM tumor samples.
- Performed comprehensive immune profiling of the TME.
Main Results:
- Identified 15 distinct immune cell subsets within PM tumors.
- Stratified PM tumors into three subgroups with significantly different survival outcomes.
- Observed that increased T and B cell infiltration, and the formation of TLS by B cells and CD4+ T cells, correlated with longer survival.
Conclusions:
- PM tumors exhibit significant heterogeneity in their immune microenvironment.
- B cells and TLS play a critical role in anti-tumor immunity in PM.
- Immune cell composition and organization, particularly B cells and TLS, are important prognostic factors in pleural mesothelioma.
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