Papaioannou Eleni, Sakellakis Minas, Melachrinou Maria, Tzoracoleftherakis Evangelos, Kalofonos Haralambos, Kourea Eleni
Department of Pathology, School of Medicine, University of Patras, Patras, Greece.
Department of Oncology, School of Medicine, University of Patras, Patras, Greece.
Anticancer Res. 2019 Mar;39(3):1217-1232. doi: 10.21873/anticanres.13232.
BACKGROUND/AIM: The role of FOXP3+ Tregs and CD8+ T-cells in different stages and subtypes of breast carcinoma (BC) is yet to be fully defined, mainly because of methodological variations between studies. The aim of this study was to assess FOXP3+ and CD8+ intratumoral stromal TILs (sTILs) by a standardized method, in order to discern differences between the histological subtypes and BC stage and evaluate the applicability of the method.
FOXP3+ and CD8+ sTILs were studied immunohistochemically in 207 BCs and counted on digital images, amounting to a standard stromal area of a 10×10 grid on ×40 magnification. The results were correlated with clinicopathological features and outcomes.
Tregs and CD8+ TILs were more abundant in HER2+ BCs (p=0.02, p=0.007, respectively), estrogen receptor (ER)-BCs (p<0.001, for both cell types), and triple-negative BCs (TNBCs) (p=0.01, p=0.006, respectively). Tregs and CD8+ TILs were associated with high grade (p<0.001 and p=0.002, respectively) and high Ki67 index (p<0.001, for both cell types). Lower CD8/FOXP3 ratio was associated with node metastases (p=0.007). Node metastases and advanced stage paralleled with decreased CD8+ sTILs (p=0.023, p=0.019, respectively). In the entire group and in ER- BCs, CD8+ TILs were associated with favorable distant metastasis-free survival (p=0.021, p<0.001, respectively), disease-free survival (p=0.022, p<0.001, respectively) and breast cancer specific survival (BCSS) (p=0.022, p=0.005). In ER-BCs, Tregs were associated with favorable BCSS (p=0.02).
Tregs and CD8+ TILs are higher in early-stage TNBCs and HER2+ BCs and diminish with progression to advanced stages. The findings provide support for immunotherapeutic manipulation of TILs, particularly in early stages of these BC subtypes. The evaluation methodology can be easily implemented for standardization of immunohistochemically-detected TILs.
背景/目的：FOXP3 +调节性T细胞（Tregs）和CD8 + T细胞在乳腺癌（BC）不同阶段和亚型中的作用尚未完全明确，主要是因为各研究之间的方法存在差异。本研究的目的是通过标准化方法评估肿瘤内基质浸润性T细胞（sTILs）中的FOXP3 +和CD8 +，以辨别组织学亚型和BC分期之间的差异，并评估该方法的适用性。
对207例BC进行免疫组织化学研究，检测FOXP3 +和CD8 + sTILs，并在数字图像上计数，相当于在40倍放大倍数下10×10网格的标准基质区域。将结果与临床病理特征和预后相关联。
Tregs和CD8 + TILs在HER2 + BC中更为丰富（分别为p = 0.02，p = 0.007），雌激素受体（ER）阴性BC中（两种细胞类型均为p <0.001），以及三阴性BC（TNBC）中（分别为p = 0.01，p = 0.006）。Tregs和CD8 + TILs与高级别相关（分别为p <0.001和p = 0.002）以及高Ki67指数（两种细胞类型均为p <0.001）。较低的CD8/FOXP3比值与淋巴结转移相关（p = 0.007）。淋巴结转移和晚期与CD8 + sTILs减少平行（分别为p = 0.023，p = 0.019）。在整个组和ER阴性BC中，CD8 + TILs与良好的无远处转移生存期（分别为p = 0.021，p <0.001）、无病生存期（分别为p = 0.022，p <0.001）和乳腺癌特异性生存期（BCSS）（分别为p = 0.022，p = 0.005）相关。在ER阴性BC中，Tregs与良好的BCSS相关（p = 0.02）。
Tregs和CD8 + TILs在早期TNBC和HER2 + BC中较高，并随着进展到晚期而减少。这些发现为TILs的免疫治疗操作提供了支持，特别是在这些BC亚型的早期阶段。该评估方法可轻松实施，以实现免疫组织化学检测TILs的标准化。
