title: Evaluation of tumour-infiltrating CD4+CD25+FOXP3+ regulatory T cells in human cutaneous benign and atypical naevi, melanomas and melanoma metastases.
abstract: BACKGROUND
  CD4+CD25+FOXP3+ regulatory T cells (Tregs) are thought to induce immunotolerance in melanoma. They have not yet been investigated in the entire spectrum of melanocytic cutaneous lesions within a tumour site.
  
  
  OBJECTIVE
  To evaluate CD4+CD25+FOXP3+ Tregs among tumour-infiltrating lymphocytes in cutaneous melanocytic lesions.
  
  
  METHODS
  We analysed 128 lesions (10 benign junctional common naevi, 10 benign compound common naevi, 10 compound Spitz naevi, 10 junctional atypical naevi, 20 compound atypical naevi, 20 radial growth phase melanomas, 30 vertical growth phase melanomas and 18 melanoma metastases). Tregs were identified by CD25-FOXP3 double immunostains.
  
  
  RESULTS
  This study indicates that CD4+/CD25+FOXP3+ Tregs are present in all groups of lesions. Junctional atypical naevi, compound atypical naevi and radial growth phase melanomas showed the highest percentages of CD4+CD25+FOXP3+ Tregs (junctional atypical naevi vs. junctional common naevi, compound common naevi, compound Spitz naevi, melanoma metastases: P < 0.0001; junctional atypical naevi vs. vertical growth phase melanomas: P = 0.001; compound atypical naevi vs. junctional common naevi, compound common naevi: P < 0.0001; compound atypical naevi vs. compound Spitz naevi, melanoma metastases: P = 0.002; compound atypical naevi vs. vertical growth phase melanomas: P = 0.02; radial growth phase melanomas vs. junctional common naevi, compound common naevi, compound Spitz naevi, melanoma metastases: P < 0.0001; radial growth phase melanomas vs. vertical growth phase melanomas: P = 0.008).
  
  
  CONCLUSIONS
  The strong prevalence of CD25+FOXP3+ Tregs both in junctional and compound atypical naevi and radial growth phase melanomas, suggests that they induce immunotolerance early during melanoma genesis, favouring melanoma growth. Their evaluation within a tumour site could be useful for prognostic and therapeutic purposes.
authors.affiliation: Department of Human Pathology and Oncology, Section of Pathological Anatomy, University of Siena, Siena 53100, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Mourmouras
authors.forename: M
authors.initials: M
authors.lastname: Fimiani
authors.forename: P
authors.initials: P
authors.lastname: Rubegni
authors.forename: M C
authors.initials: MC
authors.lastname: Epistolato
authors.forename: V
authors.initials: V
authors.lastname: Malagnino
authors.forename: C
authors.initials: C
authors.lastname: Cardone
authors.forename: E
authors.initials: E
authors.lastname: Cosci
authors.forename: M C De
authors.initials: MC
authors.lastname: Nisi
authors.forename: C
authors.initials: C
authors.lastname: Miracco
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis; D005260:Female; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000473:pathology; D008297:Male; D008545:Melanoma / Q000276:immunology*; D009508:Nevus, Pigmented / Q000276:immunology* / Q000473:pathology; D012878:Skin Neoplasms / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D014408:Biomarkers, Tumor; D015704:CD4 Antigens; D053645:Interleukin-2 Receptor alpha Subunit