Unidad de Investigación Básica y Traslacional, Oncosalud-AUNA, Lima, Peru.
Escuela de Ingeniería Biotecnológica, Universidad Católica de Santa María, Arequipa, Peru.
Sci Rep. 2018 Mar 20;8(1):4899. doi: 10.1038/s41598-018-23099-7.
Triple negative breast cancer (TNBC) is the most aggressive form of breast cancer with limited options of targeted therapy. Recent findings suggest that the clinical course of TNBC may be modified by the presence of tumor-infiltrating lymphocytes (TILs) and chemokine's expression, such as CCL5. Diverse studies have shown that CCL5 suppresses anti-tumor immunity and it has been related to poor outcome in different types of cancer while in other studies, this gene has been related with a better outcome. We sought to determine the association of CCL5 with the recruitment of TILs and other immune cells. With this aim we evaluated a retrospective cohort of 72 TNBC patients as well as publicly available datasets. TILs were correlated with residual tumor size after neoadjuvant chemotherapy (NAC) and CCL5 expression. In univariate analysis, TILs and CCL5 were both associated to the distant recurrence free survival; however, in a multivariate analysis, TILs was the only significant marker (HR = 0.336; 95%IC: 0.150-0.753; P = 0.008). CIBERSORT analysis suggested that a high CCL5 expression was associated with recruitment of CD8 T cells, CD4 activated T cells, NK activated cells and macrophages M1. The CD8A gene (encoding for CD8) was associated with an improved outcome in several public breast cancer datasets.
三阴性乳腺癌（TNBC）是最具侵袭性的乳腺癌形式，靶向治疗选择有限。最近的研究结果表明，肿瘤浸润淋巴细胞（TILs）和趋化因子的表达，如 CCL5，可能会改变 TNBC 的临床过程。多项研究表明，CCL5 抑制抗肿瘤免疫，与不同类型癌症的不良预后有关，而在其他研究中，该基因与更好的预后相关。我们试图确定 CCL5 与 TILs 和其他免疫细胞的募集之间的关联。为此，我们评估了 72 名 TNBC 患者的回顾性队列以及公开可用的数据集。TILs 与新辅助化疗（NAC）后残留肿瘤大小以及 CCL5 表达相关。在单因素分析中，TILs 和 CCL5 均与远处无复发生存相关；然而，在多因素分析中，TILs 是唯一具有显著意义的标志物（HR=0.336；95%CI：0.150-0.753；P=0.008）。CIBERSORT 分析表明，高 CCL5 表达与 CD8 T 细胞、CD4 激活 T 细胞、NK 激活细胞和巨噬细胞 M1 的募集有关。CD8A 基因（编码 CD8）与多个公共乳腺癌数据集的改善预后相关。
