Siddiqui Sameer A, Frigola Xavier, Bonne-Annee Sandra, Mercader Maria, Kuntz Susan M, Krambeck Amy E, Sengupta Shomik, Dong Haidong, Cheville John C, Lohse Christine M, Krco Christopher J, Webster W Scott, Leibovich Bradley C, Blute Michael L, Knutson Keith L, Kwon Eugene D
Department of Urology, Mayo Clinic, Rochester, Minnesota 55905, USA.
Clin Cancer Res. 2007 Apr 1;13(7):2075-81. doi: 10.1158/1078-0432.CCR-06-2139.
Regulatory T cells (Tregs) have been implicated as inhibitors of antitumoral immunity, and evidence suggests that elimination of Tregs may augment natural and pharmacologic immunity. We tested for the presence of putative Tregs within renal cell carcinoma (RCC) tumors.
We identified 170 patients who underwent radical or partial nephrectomy for clear cell RCC between 2000 and 2002. Specimens were stained with anti-CD4, anti-CD25, and anti-Foxp3 antibodies and examined using confocal microscopy. Associations of CD4(+)CD25(+)Foxp3(-) and CD4(+)CD25(+)Foxp3(+) T cells with death from RCC were evaluated using Cox proportional hazards regression models.
At last follow-up, 46 of 170 patients had died; of these, 37 died from RCC at a median of 1.4 years following nephrectomy (range, 0-4.4). Among the 124 remaining patients, median follow-up was 3.7 years (range, 0-5.7). Forty-three (25.3%) tumors harbored CD4(+)CD25(+)Foxp3(+) T cells. The presence of Foxp3(+) T cells was not significantly associated with RCC death univariately. One hundred forty-three (84.1%) tumors harbored CD4(+)CD25(+)Foxp3(-) T cells. The indicator for >or=10% CD4(+)CD25(+)Foxp3(-) T cells was significantly associated with RCC death univariately [risk ratio (RR), 2.60; 95% confidence interval (95% CI), 1.35-4.98; P = 0.004], after adjusting for tumor B7-H1 expression (RR, 2.53; 95% CI, 1.32-4.85; P = 0.005) and lymphocytic infiltration (RR, 2.53; 95% CI, 1.32-4.87; P = 0.005).
Increased presence of CD4(+)CD25(+)Foxp3(+) T cells was not significantly associated with RCC death. In contrast, CD4(+)CD25(+)Foxp3(-) T cells, which may represent a unique set of Tregs or activated helper T cells, was significantly associated with outcome.
调节性T细胞（Tregs）被认为是抗肿瘤免疫的抑制剂，有证据表明清除Tregs可能增强天然免疫和药物免疫。我们检测了肾细胞癌（RCC）肿瘤中假定Tregs的存在情况。
我们确定了2000年至2002年间因透明细胞RCC接受根治性或部分肾切除术的170例患者。标本用抗CD4、抗CD25和抗Foxp3抗体染色，并使用共聚焦显微镜检查。使用Cox比例风险回归模型评估CD4(+)CD25(+)Foxp3(-)和CD4(+)CD25(+)Foxp3(+) T细胞与RCC死亡的相关性。
在最后一次随访时，170例患者中有46例死亡；其中，37例在肾切除术后中位1.4年死于RCC（范围为0 - 4.4年）。在其余124例患者中，中位随访时间为3.7年（范围为0 - 5.7年）。43个（25.3%）肿瘤中含有CD4(+)CD25(+)Foxp3(+) T细胞。单因素分析中，Foxp3(+) T细胞的存在与RCC死亡无显著相关性。143个（84.1%）肿瘤中含有CD4(+)CD25(+)Foxp3(-) T细胞。≥10% CD4(+)CD25(+)Foxp3(-) T细胞这一指标在单因素分析中与RCC死亡显著相关[风险比（RR）为2.60；95%置信区间（95%CI）为1.35 - 4.98；P = 0.004]，在调整肿瘤B7 - H1表达（RR为2.53；95%CI为1.32 - 4.85；P = 0.005）和淋巴细胞浸润（RR为2.53；95%CI为1.32 - 4.87；P = 0.005）后依然如此。
CD4(+)CD25(+)Foxp3(+) T细胞数量增加与RCC死亡无显著相关性。相反，CD4(+)CD25(+)Foxp3(-) T细胞可能代表一组独特的Tregs或活化的辅助性T细胞，与预后显著相关。
