title: Phase- and stage-related proportions of T cells bearing the transcription factor FOXP3 infiltrate primary melanoma.
abstract: Although tumor-infiltrating lymphocytes (TILs) of primary cutaneous melanoma (PCM) include cytolytic T cells able to exert anti-PCM immunity, progression of PCM most frequently occurs, raising the hypothesis that the PCM microenvironment may also exert suppressive forces, for example, possibly developed by regulatory T (T(REG)) lymphocytes. The aim of this study was to investigate whether TILs of PCMs include lymphocytes bearing the transcription factor forkhead box protein P3 (FOXP3), which is the T(REG) lineage specification molecule in mice, and is debated to have a similar role in humans. Fourteen patients with PCM were selected, of which four had radial growth phase (RGP) stage I melanoma, five had vertical growth phase (VGP) stage I melanoma, and five had VGP stage III-IV melanoma. Formalin-fixed, paraffin-embedded sections were utilized for immunohistochemical single and double stainings. TILs of PCMs included FOXP3-bearing lymphocytes, which predominantly were CD20- and CD8-negative, but CD3-, CD4-, and CD25-positive, thus consistent with the standard immunophenotypical characteristics of "natural" T(REG) cells. Further, the proportions of FOXP3-bearing lymphocytes were higher in vertical than in RGP (P=0.001), as well as in late than in early melanoma stages (P<0.001). Should these FOXP3-bearing lymphocytes actually exert regulatory capabilities within the PCM microenvironment, they may suppress "in vivo" the local anti-PCM immune response, thus favoring melanoma progression.
authors.affiliation: Section of Dermatology, Department of Surgical Sciences, Parma University, Parma, Italy. giuseppe.depanfilis@unipr.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: De Panfilis
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Campanini
authors.forename: Marcello
authors.initials: M
authors.lastname: Santini
authors.forename: Giovanni
authors.initials: G
authors.lastname: Mori
authors.forename: Elena
authors.initials: E
authors.lastname: Tognetti
authors.forename: Roberta
authors.initials: R
authors.lastname: Maestri
authors.forename: Mara
authors.initials: M
authors.lastname: Lombardi
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Froio
authors.forename: Donata
authors.initials: D
authors.lastname: Ferrari
authors.forename: Roberto
authors.initials: R
authors.lastname: Ricci
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D019070:Cell Lineage / Q000276:immunology; D018450:Disease Progression; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D016130:Immunophenotyping; D008545:Melanoma / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D009367:Neoplasm Staging / Q000379:methods*; D012878:Skin Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology
chemical_list: D015415:Biomarkers; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors