Departments of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
Clin Cancer Res. 2010 Feb 15;16(4):1272-80. doi: 10.1158/1078-0432.CCR-09-1844. Epub 2010 Feb 9.
We hypothesized that T-cell immune interaction affects tumor development and thus clinical outcome. Therefore, we examined the clinical impact of human leukocyte antigen (HLA) class I tumor cell expression and regulatory T-cell (Treg) infiltration in breast cancer.
Our study population (N = 677) is consisted of all early breast cancer patients primarily treated with surgery in our center between 1985 and 1994. Formalin-fixed, paraffin-embedded tumor tissue was immunohistochemically stained using HCA2, HC10, and Foxp3 monoclonal antibodies.
HLA class I expression was evaluated by combining results from HCA2 and HC10 antibodies and classified into three groups: loss, downregulation, and expression. Remarkably, only in patients who received chemotherapy, both presence of Treg (P = 0.013) and higher HLA class I expression levels (P = 0.002) resulted in less relapses, independently of other variables. Treg and HLA class I were not of influence on clinical outcome in patients who did not receive chemotherapy.
We showed that HLA class I and Treg affect prognosis exclusively in chemotherapy-treated patients and are therefore one of the few predictive factors for chemotherapy response in early breast cancer patients. Chemotherapy may selectively eliminate Treg, thus enabling CTLs to kill tumor cells that have retained HLA class I expression. As a consequence, HLA class I and Treg can predict response to chemotherapy with high discriminative power. These markers could be applied in response prediction to chemotherapy in breast cancer patients.
我们假设 T 细胞免疫相互作用会影响肿瘤的发展，从而影响临床结局。因此，我们研究了人类白细胞抗原（HLA）I 类肿瘤细胞表达和调节性 T 细胞（Treg）浸润对乳腺癌的临床影响。
我们的研究人群（N=677）由 1985 年至 1994 年间在我们中心接受手术为主治疗的所有早期乳腺癌患者组成。使用 HCA2、HC10 和 Foxp3 单克隆抗体对福尔马林固定、石蜡包埋的肿瘤组织进行免疫组织化学染色。
通过结合 HCA2 和 HC10 抗体的结果，评估 HLA I 类表达，并将其分为三组：缺失、下调和表达。值得注意的是，只有在接受化疗的患者中，Treg 的存在（P=0.013）和更高的 HLA I 类表达水平（P=0.002）与更少的复发独立相关，与其他变量无关。在未接受化疗的患者中，Treg 和 HLA I 类对临床结局没有影响。
我们表明，HLA I 类和 Treg 仅在接受化疗的患者中影响预后，因此是早期乳腺癌患者化疗反应的少数预测因素之一。化疗可能选择性地消除 Treg，从而使 CTL 能够杀死保留 HLA I 类表达的肿瘤细胞。因此，HLA I 类和 Treg 可以用高判别力预测对化疗的反应。这些标志物可应用于预测乳腺癌患者对化疗的反应。
