Intense Foxp3+CD25+ regulatory T‐cell infiltration is associated with high‐grade cutaneous squamous cell carcinoma and counterbalanced by CD8+/Foxp3+CD25+ ratio. (1st January 2015)

• Record Type: Journal Article
• Authors: Azzimonti, B.; Zavattaro, E.; Provasi, M.; Vidali, M.; Conca, A.; Catalano, E.; Rimondini, L.; Colombo, E.; Valente, G.
• Is Part Of: British journal of dermatology. Volume 172:Number 1(2015:Jan.)
• Page Start: 64
• Page End: 73
• Publication Date: 2015-01-01
• Subjects: Dermatology -- Periodicals; Skin -- Diseases -- Periodicals; 616.5
• DOI: 10.1111/bjd.13172
• Languages: English
• ISSNs: 0007-0963

Abstract

Summary: Background: Recent reports have revealed the therapeutic potential of cell‐mediated immunity in neoplasms such as cutaneous squamous cell carcinoma (SCC). Objectives: To define the antigenic coexpression of regulatory T cells (Tregs) and plasmacytoid dendritic cells (pDCs) and assess the CD8 + /Foxp3 + CD25 + cell ratio at peritumoral and intratumoral levels in order to investigate a correlation with the aggressiveness of SCC tumours. Methods: We evaluated the content and distribution of Foxp3 + CD25 + Treg and CD123 + pDC infiltration and assessed CD8 + /Foxp3 + CD25 + cell ratio at peritumoral and intratumoral levels in 40 SCCs (20 well‐differentiated, G1; and 20 moderately to poorly differentiated, G2–G3) to investigate a correlation with their aggressiveness. We determined the profiles of Tregs and CD123 + cells; immunostained for CD4, CD8, CD123, interleukin (IL)‐1 and transforming growth factor (TGF)‐β1; and unequivocally double stained for Foxp3CD25. Results: Peritumorally, CD4, CD8 and Foxp3 expression showed no difference between the two groups. CD123 + cells were fewer in 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 trend in this group of activated T lymphocytes towards total Treg Foxp3 + cells, while the CD8 + /Foxp3 + CD25 + ratio was higher in G1 ( 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 Foxp3CD25, TGF‐β1 and IL‐10, they were less expressed in G1, whereas they were positive in G2–G3 ( P < 0·05). The CD8 + /Foxp3 + CD25 + ratio was similar to that observed in peritumoral infiltration. Conclusions: Our data suggest that intratumoral recruitment of Tregs, high expression of TGF‐β1 and IL‐10, almost negative CD123+, and a low CD8 + /Foxp3 + CD25 + T‐cell ratio may contribute to the aggressiveness of cutaneous SCC, as already evidenced for other solid tumours.