Chronic lymphocytic thyroiditis (CLT) has a positive prognostic value in papillary thyroid cancer (PTC) patients: the potential key role of Foxp3+ T lymphocytes

J Endocrinol Invest. 2018 Jun;41(6):703-709. doi: 10.1007/s40618-017-0794-8. Epub 2017 Dec 11.


Background: An impact of chronic lymphocytic thyroiditis (CLT) on papillary thyroid cancer (PTC) outcome has long been advocated but it is still controversial.

Purpose: The aim of this study was to evaluate the prognostic value of CLT in a retrospective cohort of PTC patients and to characterize the lymphocytic subpopulations and infiltrate (LI).

Materials and methods: We assessed 375 PTC patients, aged 45.2 ± 16.4 years, and treated with thyroidectomy and radioiodine remnant ablation, with a mean follow-up of 6.28 ± 3.86 years. In a subgroup of patients (n = 81) tissue sections were reviewed for the presence of CLT or lymphocytes associated with tumor in absence of background thyroiditis (TAL); cytotoxic CD8+/regulatory Foxp3+ T lymphocyte (CD8+/Foxp3+) ratio was characterized by immunohistochemistry: a low ratio is suggestive of a less effective anti tumor immune response.

Results: Seventy-five/375 patients (20%) had a histological diagnosis of CLT and showed at the last follow-up a significantly better outcome compared to those with no CLT (cure rate: 91.8 versus 76.3%, p = 0.003). LI was characterized in 81 PTC patients (24 with CLT and 57 with TAL): the peri-tumoral CD8+/Foxp3+ ratio was lower in patients not cured at the final evaluation.

Conclusions: Our data suggest that concurrent CLT has a protective effect on PTC outcome and that the imbalance between cytotoxic and regulatory T lymphocytes in the peri-tumoral TAL may affect the tumor-specific immune response favoring a more aggressive behavior of cancer.

Keywords: Cancer; Foxp3; Prognosis; Thyroiditis.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Papillary / complications
  • Carcinoma, Papillary / immunology*
  • Carcinoma, Papillary / surgery
  • Child
  • Child, Preschool
  • Female
  • Follow-Up Studies
  • Forkhead Transcription Factors / metabolism*
  • Hashimoto Disease / complications
  • Hashimoto Disease / immunology*
  • Hashimoto Disease / surgery
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Retrospective Studies
  • T-Lymphocytes / immunology*
  • Thyroid Neoplasms / complications
  • Thyroid Neoplasms / immunology*
  • Thyroid Neoplasms / surgery
  • Thyroidectomy*
  • Young Adult


  • FOXP3 protein, human
  • Forkhead Transcription Factors