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Tertiary Lymphoid Structures Across Organs: Context, Composition, and Clinical Levers.

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Tertiary lymphoid structures (TLSs) form in non-lymphoid tissues during chronic inflammation. This review covers their formation, function, clinical relevance in disease, and new high-resolution analysis methods for therapeutic targeting.

Keywords:
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Area of Science:

  • Immunology
  • Pathology
  • Cell Biology

Background:

  • Tertiary lymphoid structures (TLSs) are immune cell aggregates found in non-lymphoid tissues during chronic inflammation and persistent antigen exposure.
  • TLSs exhibit a spectrum of development, from simple immune cell clusters to organized structures with functional germinal centers (GC).

Purpose of the Study:

  • To provide a comprehensive review of Tertiary lymphoid structures (TLSs) formation, architecture, and function across various tissues.
  • To explore the clinical significance and dual roles of TLSs in health and disease, including infections, autoimmunity, cancer, and allergy.
  • To discuss emerging technologies for high-resolution TLS analysis and therapeutic modulation.

Main Methods:

  • Literature review and synthesis of existing research on TLSs.
  • Analysis of TLS formation, structure, and function in diverse tissue contexts.
  • Exploration of clinical data linking TLSs to various pathologies and immune responses.

Main Results:

  • TLSs are found in numerous organs and vary in maturity and organization, with both shared and tissue-specific characteristics.
  • TLSs play complex roles in disease, contributing to both protective immunity and pathological processes.
  • Advanced technologies like spatial multi-omics and digital pathology offer new avenues for dissecting TLS biology.

Conclusions:

  • Understanding TLS maturation and tissue context is crucial for interpreting their clinical associations.
  • TLSs represent potential therapeutic targets for modulating immune responses in various diseases.
  • Emerging high-resolution techniques will advance the study and clinical application of TLS-targeted therapies.