1. ¹Section of Dermatology, Department of Surgical Sciences, Parma University, Parma, Italy
2. ²Section of Pathology, Department of Pathology and Laboratory Medicine, Parma University, Parma, Italy
3. ³Department of General and Inorganic Chemistry, Analytical Chemistry and Physical Chemistry, Parma University, Parma, Italy

Correspondence: Professor Giuseppe De Panfilis, Clinica Dermatologica Università di Parma, Via Gramsci 14, Parma I-43100, Italy. E-mail: giuseppe.depanfilis@unipr.it

Received 27 March 2007; Revised 15 June 2007; Accepted 5 July 2007; Published online 13 September 2007.

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.