title: Glucocorticoid-induced tumor necrosis factor receptor expression in patients with cervical human papillomavirus infection.
abstract: BACKGROUND
  The progression of human papillomavirus (HPV) infection in the anogenital tract has been associated with the involvement of cells with regulatory properties. Evidence has shown that glucocorticoid-induced tumor necrosis factor receptor (GITR) is an important surface molecule for the characterization of these cells and proposes that GITR ligand may constitute a rational treatment for many cancer types. We aimed to detect the presence of GITR and CD25 in cervical stroma cells with and without pathological changes or HPV infection to better understand the immune response in the infected tissue microenvironment.
  
  
  METHODS
  We subjected 49 paraffin-embedded cervical tissue samples to HPV DNA detection and histopathological analysis, and subsequently immunohistochemistry to detect GITR and CD25 in lymphocytes.
  
  
  RESULTS
  We observed that 76.9% of all samples with high GITR expression were HPV-positive regardless of histopathological findings. High GITR expression (77.8%) was predominant in samples with ≥ 1,000 RLU/PCB. Of the HPV-positive samples negative for intraepithelial lesion and malignancy, 62.5% had high GITR expression. High GITR expression was observed in both carcinoma and high-grade squamous intraepithelial lesion (HSIL) samples (p = 0.16). CD25 was present in great quantities in all samples.
  
  
  CONCLUSIONS
  The predominance of high GITR expression in samples with high viral load that were classified as HSIL and carcinoma suggests that GITR+ cells can exhibit regulatory properties and may contribute to the progression of HPV-induced cervical neoplasia, emphasizing the importance of GITR as a potential target for immune therapy of cervical cancer and as a disease evolution biomarker.
authors.affiliation: Programa de Pós-Graduação em Saúde e Desenvolvimento da Região Centro-Oeste, Faculdade de Medicina, Universidade Federal de Mato Grosso do Sul, Campo Grande, MS, Brazil.
authors.forename: Cacilda Tezelli Junqueira
authors.initials: CT
authors.lastname: Padovani
authors.forename: Camila Mareti
authors.initials: CM
authors.lastname: Bonin
authors.forename: Inês Aparecida
authors.initials: IA
authors.lastname: Tozetti
authors.forename: Alda Maria Teixeira
authors.initials: AM
authors.lastname: Ferreira
authors.forename: Carlos Eurico dos Santos
authors.initials: CE
authors.lastname: Fernandes
authors.forename: Izaias Pereira da
authors.initials: IP
authors.lastname: Costa
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis; D018450:Disease Progression; D005260:Female; D053450:Glucocorticoid-Induced TNFR-Related Protein / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis*; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000150:complications / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D002578:Uterine Cervical Dysplasia / Q000276:immunology / Q000821:virology*; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000821:virology*
chemical_list: D014408:Biomarkers, Tumor; D053450:Glucocorticoid-Induced TNFR-Related Protein; D053645:Interleukin-2 Receptor alpha Subunit