Excellence Center for Research, Transfer, and High Education DENOTHE, Department Of Urology, University Of Florence, Florence, Italy.
BJU Int. 2011 May;107(9):1500-6. doi: 10.1111/j.1464-410X.2010.09555.x. Epub 2010 Aug 24.
• To compare the frequency of T regulatory cells (Tregs) in peripheral blood of patients (pPB) affected by renal cell carcinoma (RCC) both with the frequency of Tregs found in PB of healthy donors (hPB) and that of Tregs present in tumour infiltrating lymphocytes (TILs). To verify in vitro the inhibitory activity of tumour isolated Tregs on the effector T cells and, finally, to assess the prognostic role of Treg frequency determination.
• Treg frequency in hPB, pPB and TILs was evaluated in 30 patients and 20 healthy controls by measuring both membrane-CD25 and intracytoplasmic-Foxp3 expression by flow cytometry. • Treg inhibitory activity was evaluated by an in vitro proliferation assay performed on total, CD25-depleted mononuclear cells (MNC) and CD25-depleted MNC cultured in the presence of purified CD25(+) Tregs. • Finally, Treg frequency in pPB and TIL were correlated with conventional prognostic factors and scores of University of California Los Angeles and Kattan predictive models.
• Treg frequency was higher in TILs than in pPB (P= 0.002), whereas there were no important differences between hPB and pPB. CD25(+) cells isolated either from PB and tumours showed the ability to significantly suppress in vitro both proliferation and interferon-γ production by CD25-depleted MNC, thus demonstrating that they are active Tregs. • Treg frequency was found to significantly correlate both with pathological stage (pPB, P= 0.03; TIL, P= 0.04) and nuclear grade (TIL, P= 0.005), both for UCLA and Kattan models (all: P < 0.05 for both pPB and TIL).
• Treg frequency is significantly higher in TIL than in pPB of patients with RCC. Tregs showed in vitro an inhibitory activity on effector T cells isolated from kidney tumours. The increase in both peripheral and intratumoral Tregs in subjects affected with RCC were associated with worse prognosis.
比较外周血受肾细胞癌（RCC）影响的患者（pPB）和健康供者（hPB）外周血中 T 调节细胞（Tregs）的频率以及肿瘤浸润淋巴细胞（TILs）中 Tregs 的频率。验证肿瘤分离的 Tregs 对效应 T 细胞的体外抑制活性，最后评估 Treg 频率测定的预后作用。
通过流式细胞术测量膜 CD25 和细胞内 Foxp3 的表达，评估 30 例患者和 20 例健康对照者 hPB、pPB 和 TILs 中的 Treg 频率。通过总单核细胞（MNC）、CD25 耗竭的 MNC 和 CD25 耗竭的 MNC 在纯化的 CD25(+)Tregs 存在下培养的体外增殖试验评估 Treg 抑制活性。最后，将 pPB 和 TIL 中的 Treg 频率与传统的预后因素和加利福尼亚大学洛杉矶分校和卡坦预测模型的评分相关联。
TIL 中的 Treg 频率高于 pPB（P=0.002），而 hPB 与 pPB 之间没有重要差异。从 PB 和肿瘤中分离的 CD25(+)细胞均显示出显著抑制 CD25 耗竭的 MNC 体外增殖和干扰素-γ产生的能力，从而表明它们是活性 Tregs。Treg 频率与病理分期（pPB，P=0.03；TIL，P=0.04）和核分级（TIL，P=0.005）均显著相关，UCLA 和 Kattan 模型均如此（pPB 和 TIL 均为所有：P<0.05）。
RCC 患者 TIL 中的 Treg 频率明显高于 pPB。Tregs 在体外对肾脏肿瘤中分离的效应 T 细胞具有抑制活性。受 RCC 影响的受试者外周血和肿瘤内 Tregs 的增加与预后较差相关。
