title: Phenotypical analysis of lymphocytes with suppressive and regulatory properties (Tregs) and NK cells in the papillary carcinoma of thyroid.
abstract: BACKGROUND
  The immune system seems to play a key role in preventing metastasis and recurrence of thyroid cancer. T regulatory lymphocytes (Tregs) and natural killer (NK) cells play an important role in the dysfunction of the host immune system in cancer patients.
  
  
  OBJECTIVE
  We investigated thyroid gland infiltration by Tregs and NK cells in patients with papillary thyroid cancer (PTC) and thyroid nodular goiter (TNG). The correlation between the extent of the disease and the lymphocytic infiltration of Tregs and NK cells was examined.
  
  
  METHODS
  A total of 65 patients with PTC, 25 with TNG, and 50 healthy controls were studied. Blood and tissue samples from 28 patients with PTC and 13 with TNG and blood samples from the healthy controls were analyzed for T4 (CD3(+)CD4(+)), T8 (CD3(+)CD8(+)), NK (CD3(-)CD16(+)CD56(+)), and CD4(+)CD25(+)CD127(-/low) Tregs by flow cytometry (FC). Tissue samples were also analyzed for Foxp3(+) Tregs by immunohistochemistry.
  
  
  RESULTS
  Tregs showed greater infiltration in thyroid tissue of PTC patients compared with patients with TNG (P < 0.0009 for FC and P < 0.0001 for immunohistochemistry); FC analysis of blood samples showed no difference between the groups. Flow cytometry analysis showed significantly increased NK cells in PTC tissue compared with TNG tissue (P = 0.037), whereas blood samples showed no difference. CD4(+) and CD8(+) T cells did not differ in blood and tissue samples. Increased Tregs tissue infiltration was positively correlated with advanced disease stage (P < 0.0026), whereas NK infiltration was negatively correlated (P < 0.0041).
  
  
  CONCLUSIONS
  Tregs and NK cells may be important regulators of thyroid cancer progression.
authors.affiliation: Department of Pharmacology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece.
authors.forename: Foteini
authors.initials: F
authors.lastname: Gogali
authors.forename: George
authors.initials: G
authors.lastname: Paterakis
authors.forename: George Z
authors.initials: GZ
authors.lastname: Rassidakis
authors.forename: Gregory
authors.initials: G
authors.lastname: Kaltsas
authors.forename: Chrysoula I
authors.initials: CI
authors.lastname: Liakou
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Gousis
authors.forename: Evangelos
authors.initials: E
authors.lastname: Neonakis
authors.forename: Menelaos N
authors.initials: MN
authors.lastname: Manoussakis
authors.forename: Charis
authors.initials: C
authors.lastname: Liapi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002291:Carcinoma, Papillary / Q000276:immunology* / Q000473:pathology; D005260:Female; D006044:Goiter, Nodular / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D013961:Thyroid Gland / Q000276:immunology / Q000473:pathology; D013964:Thyroid Neoplasms / Q000276:immunology* / Q000473:pathology