A low number of tumor-infiltrating FOXP3-positive cells during primary systemic chemotherapy correlates with favorable anti-tumor response in patients with breast cancer
A low number of tumor-infiltrating FOXP3-positive cells during primary systemic chemotherapy correlates with favorable anti-tumor response in patients with breast cancer
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DOI：
10.3892/or_00000434
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发表时间：
2009-08-01
期刊：
影响因子：
4.2
通讯作者：
Kuroi, Katsumasa
中科院分区：
文献类型：
--
作者：
Aruga, Tomoyuki;Suzuki, Eiji;Kuroi, Katsumasa
癌细胞诱导免疫抑制细胞的增殖和局部积累，例如称为调节性T细胞（TCFs）的FOXP 3阳性细胞，导致肿瘤诱导的免疫耐受。尽管癌症化疗通常被认为是免疫抑制的，但一些化疗剂激活抗癌免疫应答。因此，我们推测原发性全身化疗（PSC）期间肿瘤浸润FOXP 3阳性细胞的数量与乳腺癌患者的治疗结果相关。2000年9月至2005年1月，我们检查了93例乳腺癌患者诊断的芯针活检和PSC治疗。用FOXP 3小鼠单克隆抗体对空芯针活检（CNB）和手术切除的标本进行染色，以比较PSC前后肿瘤中FOXP 3阳性细胞的数量。中位临界值>16.3/高倍视野（HPF）和>6.6/HPF分别定义了CNB和手术标本中的高数量THBE。然后，我们将患者分为4组（HH，CNB和手术标本中FOXP 3阳性细胞数量较高; LL，两种标本中FOXP 3阳性细胞数量较低; HL，CNB中FOXP 3阳性细胞数量较高，手术标本中FOXP 3阳性细胞数量较低; LH，CNB中FOXP 3阳性细胞数量较低，手术标本中FOXP 3阳性细胞数量较高）。PSC后淋巴管侵袭阳性、临床无应答和ER阴性肿瘤含有显著更多的FOXP 3阳性细胞（分别为p=0.04、p=0.03和p=0.04）。在CNB和手术切除标本中，FOXP 3阳性细胞数量少的患者预后好于FOXP 3阳性细胞数量多的患者。在多因素分析中，LL组的无复发生存率显著高于非LL组（LH、HL和HH），风险比为5.81（95%CI，1.09-07.5; p=0.04）。这些发现表明，在PSC期间鉴定的FOXP 3阳性细胞的数量代表了一个有希望的预测因素，也可能是乳腺癌的重要治疗靶点。
Cancer cells induce proliferation and local accumulation of immunosuppressive cells, such as FOXP3-positive cells known as regulatory T cells (Tregs), leading to tumor-induced immune tolerance. Although cancer chemotherapy is usually considered immunosuppressive, some chemotherapeutic agents activate an anticancer immune response. Therefore, we postulated that the number of tumor-infiltrating FOXP3-positive cells during primary systemic chemotherapy (PSC) correlates with therapeutic outcomes in patients with breast cancer. Between September 2000 and January 2005, we examined 93 patients with breast cancer diagnosed by core-needle biopsy and treated with PSC. Core-needle biopsy (CNB) and surgical resected specimens were stained with a FOXP3 mouse monoclonal antibody to compare the numbers of FOXP3-positive cells in the tumors before and after PSC. A median cut-off value of >16.3/high power field (HPF) and >6.6/HPF defined high numbers of Tregs in CNB and in surgical specimens, respectively. We then assigned the patients into 4 groups (HH, high number of FOXP3-positive cells in both CNB and surgical specimen; LL, low number in both specimens; HL, high in CNB and low in the surgical specimen; LH, low in CNB and high in surgical specimen). Lymph vessel invasion-positive, clinically non-responder and ER-negative tumors contained significantly more FOXP3-positive cells after PSC (p=0.04, p=0.03 and p=0.04, respectively). Prognosis was better among patients with low numbers than high numbers of FOXP3-positive cells both in CNB and in surgically resected specimens. In multivariate analysis, LL group demonstrated significantly better recurrence-free survival with risk ratio of 5.81 (95%CI, 1.09-07.5; p=0.04) rather than that of non-LL group (LH, HL and HH). These findings suggest that the number of FOXP3-positive cells identified during PSC represents a promising predictive factor that might also be an important therapeutic target for breast cancer.