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Tertiary lymphoid structures in thyroid cancer.

Katia Sakimi Nakadaira1, Kelly Cristina Saito1, Cesar Seigi Fuziwara1

  • 1Departamento de Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brasil.

Archives of Endocrinology and Metabolism
|September 26, 2025
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Summary
This summary is machine-generated.

Tertiary lymphoid structures (TLSs) were found in 41% of papillary thyroid carcinoma (PTC) samples, with B cells present in mature TLSs. These findings suggest TLSs may serve as immunobiomarkers in thyroid cancer.

Keywords:
Papillary thyroid carcinomalymphoid neogenesismorphological analysistertiary lymphoid structure maturationtumor-infiltrating B cells

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Area of Science:

  • Oncology
  • Immunology
  • Pathology

Background:

  • Tertiary lymphoid structures (TLSs) are organized immune cell aggregates found in non-lymphoid tissues during chronic inflammation or infection.
  • Their presence in the tumor microenvironment (TME) is increasingly recognized for its role in modulating anti-tumor immunity.
  • Understanding TLS formation and composition in thyroid cancer is crucial for developing novel immunotherapeutic strategies.

Purpose of the Study:

  • To investigate the presence, location, and maturation status of tertiary lymphoid structures (TLSs) in papillary thyroid carcinoma (PTC).
  • To identify tumor-infiltrating B cells within the germinal centers of TLSs in the PTC TME.
  • To correlate TLS presence with clinical and molecular characteristics of PTC.

Main Methods:

  • Morphological assessment of hematoxylin and eosin-stained histological samples from 112 PTC patients.
  • Immunofluorescence staining to detect B cells within mature TLSs.
  • Analysis of 499 scanned slides from The Cancer Genome Atlas - Thyroid Carcinoma (TCGA-THCA) dataset via cBioPortal.

Main Results:

  • TLSs were identified in 41% of PTC samples, with most located in peritumoral regions.
  • Mature TLSs containing B cells and germinal centers were observed in 15% of cases.
  • TLSs were found in 8.4% of TCGA-THCA cases, often associated with the BRAFV600E mutation and elevated immune markers.

Conclusions:

  • TLSs are present in the tumor microenvironment of papillary thyroid carcinoma.
  • The morphological characterization of TLSs and their B cell content offers potential as immunobiomarkers.
  • TLSs may play a significant role in modulating tumor-immune interactions in thyroid cancer.