Intense Foxp3+CD25+ regulatory T‐cell infiltration is associated with high‐grade cutaneous squamous cell carcinoma and counterbalanced by CD8+/Foxp3+CD25+ ratio. (30th November 2014)

• 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: 2014-11-30
• Subjects: Dermatology -- Periodicals; Skin -- Diseases -- Periodicals; 616.5
• DOI: 10.1111/bjd.13172
• Languages: English
• ISSNs: 0007-0963

Abstract

<abstract abstract-type="main" id="bjd13172-abs-0001"> <title>Summary</title> <sec id="bjd13172-sec-0001" sec-type="section"> <title>Background</title> <p>Recent reports have revealed the therapeutic potential of cell‐mediated immunity in neoplasms such as cutaneous squamous cell carcinoma (SCC).</p> </sec> <sec id="bjd13172-sec-0002" sec-type="section"> <title>Objectives</title> <p>To define the antigenic coexpression of regulatory T cells (Tregs) and plasmacytoid dendritic cells (pDCs) and assess the CD8<sup>+</sup>/Foxp3<sup>+</sup>CD25<sup>+</sup> cell ratio at peritumoral and intratumoral levels in order to investigate a correlation with the aggressiveness of SCC tumours.</p> </sec> <sec id="bjd13172-sec-0003" sec-type="section"> <title>Methods</title> <p>We evaluated the content and distribution of Foxp3<sup>+</sup>CD25<sup>+</sup> Treg and CD123<sup>+</sup> pDC infiltration and assessed CD8<sup>+</sup>/Foxp3<sup>+</sup>CD25<sup>+</sup> 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<sup>+</sup> cells; immunostained for CD4, CD8, CD123, interleukin (IL)‐1 and transforming growth factor (TGF)‐β1; and unequivocally double stained for Foxp3CD25.</p> </sec> <sec id="bjd13172-sec-0004" sec-type="section"> <title>Results</title> <p>Peritumorally, CD4, CD8 and Foxp3 expression showed no difference between the two groups. CD123<sup>+</sup> cells were fewer in G2–G3 (<italic>P </italic>=<italic> </italic>0·0005), while Foxp3<sup>+</sup>CD25<sup>+</sup> cells were more numerous (<italic>P </italic>=<italic> </italic>0·0005). The Foxp3<sup>+</sup>CD25<sup>+</sup>/Foxp3<sup>+</sup> ratio was higher in G2–G3 cases (<italic>P </italic>=<italic> </italic>0·0005), confirming the trend in this group of activated T lymphocytes towards total Treg Foxp3<sup>+</sup> cells, while the CD8<sup>+</sup>/Foxp3<sup>+</sup>CD25<sup>+</sup> ratio was higher in G1 (<italic>P </italic>=<italic> </italic>0·0005). Intratumorally, CD4<sup>+</sup> and CD8<sup>+</sup> cells infiltrated G2–G3 (<italic>P </italic>=<italic> </italic>0·048) more than G1 (<italic>P </italic>=<italic> </italic>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 (<italic>P </italic><<italic> </italic>0·05). The CD8<sup>+</sup>/Foxp3<sup>+</sup>CD25<sup>+</sup> ratio was similar to that observed in peritumoral infiltration.</p> </sec> <sec id="bjd13172-sec-0005" sec-type="section"> <title>Conclusions</title> <p>Our data suggest that intratumoral recruitment of Tregs, high expression of TGF‐β1 and IL‐10, almost negative CD123+, and a low CD8<sup>+</sup>/Foxp3<sup>+</sup>CD25<sup>+</sup> T‐cell ratio may contribute to the aggressiveness of cutaneous SCC, as already evidenced for other solid tumours.</p> </sec> </abstract>