Intense Foxp3+CD25+regulatory T cell infiltration is associated with high-grade cutaneous squamous cell carcinoma and counterbalanced by CD8+/Foxp3+CD25+ratio

Recent reports revealed the therapeutic potential of cell-mediated immunity in neoplasms like cutaneous squamous cell carcinomas (SCC).We evaluated the content and distribution of Foxp3+CD25+ regulatory T and CD123+ plasmacytoid dendritic cells infiltration and assessed CD8+/Foxp3+CD25+ cell ratio at peritumoral and intratumoral levels in 40 SCC (20 well-differentiated G1, and 20 moderately to poorly-differentiated G2-G3) to evidence a correlation with their aggressiveness. We determined the profiles of Tregs and CD123+ cells and also run an immunostaining for CD4, CD8, CD123, IL-10, TGF-beta 1 and an unequivocal double staining for Foxp3CD25. Peritumorally, CD4, CD8 and Foxp3 expression showed no difference between the two groups. CD123+ cells were fewer in the G2-G3 (p= 0.0005) while Foxp3+CD25+ cells were more numerous (p=0.0005). The Foxp3+CD25+/Foxp3+ ratio was higher in G2-G3 cases (p=0.0005), confirming the prevalence in this group of activated T lymphocytes towards total regulatory T Foxp3+ cells, while the CD8+/Foxp3+CD25+ ratio was higher in G1 specimens (p=0.0005). Intratumorally, CD4+ and CD8+ cells infiltrated G2-G3 (p=0.048) more than G1 (p=0.004), whereas almost all cells were CD123 negative. Regarding Foxp3+CD25+, TGF-beta 1+ and IL-10+ , they were less expressed in G1, whereas G2-G3 were positive (p<0.05). The result of CD8+/Foxp3+CD25+ ratio was similar to that observed in the peritumoral infiltration. Our data suggest that an intratumoral recruitment of Tregs, a high expression of TGF-beta 1 and IL-10, an almost negative CD123+ cells finding, and a low CD8+/Foxp3+CD25+ T cell ratio may contribute to the aggressiveness of cutaneous SCC as already evidenced for other solid tumors.