Foxp3+ CD25+ 调节性 T 细胞浸润强烈与高级别皮肤鳞状细胞癌相关，并且与 CD8+/Foxp3+ CD25+ 比值相平衡。

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

机构信息

Department of Health Sciences, Medical School, University of Piemonte Orientale 'A. Avogadro', 28100, Novara, Italy.

出版信息

Br J Dermatol. 2015 Jan;172(1):64-73. doi: 10.1111/bjd.13172. Epub 2014 Nov 30.

DOI:10.1111/bjd.13172

PMID:24910265

Abstract

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.

摘要

背景

最近的报告揭示了细胞介导的免疫在皮肤鳞状细胞癌（SCC）等肿瘤中的治疗潜力。

目的

定义调节性 T 细胞（Tregs）和浆细胞样树突状细胞（pDC）的抗原共表达，并评估肿瘤周围和肿瘤内 CD8（+）/Foxp3（+）CD25（+）细胞比值，以研究其与 SCC 肿瘤侵袭性的相关性。

方法

我们评估了 Foxp3（+）CD25（+）Treg 和 CD123（+）pDC 浸润的含量和分布，并评估了 40 例 SCC（20 例分化良好，G1；20 例中至差分化，G2-G3）肿瘤周围和肿瘤内 CD8（+）/Foxp3（+）CD25（+）细胞比值，以研究其与侵袭性的相关性。我们确定了 Tregs 和 CD123（+）细胞的表型；免疫染色 CD4、CD8、CD123、白细胞介素（IL）-1 和转化生长因子（TGF）-β1；并明确地对 Foxp3CD25 进行了双重染色。

结果

肿瘤周围，两组之间 CD4、CD8 和 Foxp3 的表达没有差异。G2-G3 组的 CD123（+）细胞较少（P=0.0005），而 Foxp3（+）CD25（+）细胞较多（P=0.0005）。G2-G3 组 Foxp3（+）CD25（+）/Foxp3（+）比值较高（P=0.0005），证实了该组活化 T 淋巴细胞向总 Treg Foxp3（+）细胞的趋势，而 G1 组 CD8（+）/Foxp3（+）CD25（+）比值较高（P=0.0005）。肿瘤内，CD4（+）和 CD8（+）细胞浸润 G2-G3（P=0.048）多于 G1（P=0.004），而几乎所有细胞均为 CD123 阴性。关于 Foxp3CD25、TGF-β1 和 IL-10，它们在 G1 中表达较低，而在 G2-G3 中表达阳性（P<0.05）。CD8（+）/Foxp3（+）CD25（+）比值与肿瘤周围浸润观察到的比值相似。