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.

Abstract

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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