Hospital de Gineco Obstetricia No. 3 del Centro Médico Nacional la Raza del Instituto Mexicano del Seguro Social, Ciudad de México, México.
Unidad de morfología y función (UMF), Facultad de Estudios Superiores Iztacala de la Universidad Nacional Autónoma de México, Ave. De los Barrios No. 1., 54090, Tlalnepantla, Estado de México, México.
Breast Cancer. 2020 Sep;27(5):837-849. doi: 10.1007/s12282-020-01079-y. Epub 2020 Mar 16.
Tumor-infiltrating lymphocytes are an important component of the tumor microenvironment (TME) in breast cancer. They have been linked with tumor pathogenesis in advanced stages. However, little is known about their contribution in early phases. In this study, we analyzed the infiltration of leukocytes and cancer stem cells (CSC) in tumors from patients with early breast cancer.
Samples of blood and tumor tissue from 30 patients with breast cancer were collected, and the number of dendritic cells (DC), T cells, and CSC were analyzed by flow cytometry.
Tumor-infiltrating CD4 and CD8 T cells expressed higher levels of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) compared with peripheral T cells. Regulatory T cells (Treg) were enriched in tumors and overexpressed glucocorticoid-induced TNFR-related protein and CTLA-4. Tumor Treg had a positive correlation with the amount of myeloid DC (mDC) and disease progression. The CD8/Treg ratio was associated with lymph node metastasis and tumor stages. The main subset of DC in early breast tumors was mDC, while plasmacytoid DC were almost absent. CSC were present in most tumors with higher frequencies in patients with lymph node metastasis. CSC were also associated with the amount of tumor-infiltrating Treg.
Early breast cancer has an inflammatory milieu characterized by mDC, Treg, and CSC infiltration. The frequencies of Treg, CSC and CD8/Treg ratio were associated with disease progression. The composition of leukocytes and the presence of CSC in early breast tumors should be considered for the development of new therapeutic approaches.
肿瘤浸润淋巴细胞是乳腺癌肿瘤微环境（TME）的重要组成部分。它们与晚期肿瘤的发病机制有关。然而，对于它们在早期阶段的贡献知之甚少。在这项研究中，我们分析了早期乳腺癌患者肿瘤中白细胞和癌症干细胞（CSC）的浸润情况。
收集了 30 名乳腺癌患者的血液和肿瘤组织样本，并通过流式细胞术分析树突状细胞（DC）、T 细胞和 CSC 的数量。
与外周 T 细胞相比，肿瘤浸润的 CD4 和 CD8 T 细胞表达更高水平的细胞毒性 T 淋巴细胞相关抗原 4（CTLA-4）。调节性 T 细胞（Treg）在肿瘤中富集，并过度表达糖皮质激素诱导的 TNFR 相关蛋白和 CTLA-4。肿瘤 Treg 与髓样 DC（mDC）的数量和疾病进展呈正相关。CD8/Treg 比值与淋巴结转移和肿瘤分期相关。早期乳腺癌的主要 DC 亚群是 mDC，而浆细胞样 DC 几乎不存在。CSC 存在于大多数肿瘤中，在有淋巴结转移的患者中频率更高。CSC 还与肿瘤浸润 Treg 的数量相关。
早期乳腺癌具有以 mDC、Treg 和 CSC 浸润为特征的炎症微环境。Treg、CSC 和 CD8/Treg 比值的频率与疾病进展相关。早期乳腺癌肿瘤中白细胞的组成和 CSC 的存在应考虑用于开发新的治疗方法。
