Laboratory of Molecular Immunology and Immunobiotechnology, M.A. Aitkhozhin's Institute of Molecular Biology and Biochemistry, 86 Dosmuhamedov Str., Almaty, 050012, Kazakhstan.
Laboratory of Flow Cytometry, Scientific Center for Pediatrics and Children's Surgery, 146 Al-Farabi Str., Almaty, 050044, Kazakhstan.
Breast Cancer. 2018 Nov;25(6):687-697. doi: 10.1007/s12282-018-0874-4. Epub 2018 May 24.
Regulatory T cells (Tregs) play a major role in tumor escape from immunosurveillance by suppressing effector cells. The number of Tregs is increased in tumor sites and peripheral blood of breast cancer patients. However, the data regarding phenotypic and functional heterogeneity of Treg subpopulations in breast cancer are limited. The present study aimed to investigate the number and suppressive potential of Tregs that possess natural naïve-(N nTregs), effector/memory-like (EM nTregs), and Tr1-like phenotypes in breast cancer patients and healthy women.
The study included 10 HW and 17 primary breast cancer patients. Numbers of CD4CD25FoxP3CD45RA N nTregs, CD4CD25FoxP3CD45RA EM nTregs, and CD4IL-4IL-10 Tr1 subsets and the expression of CTLA-4, CD39, GITR, LAP, and IL-35 by these Treg subsets were measured in freshly obtained peripheral blood by flow cytometry.
Herein, we demonstrate that the percentages of N nTregs, EM nTregs, CD25 and FoxP3 Tr1 cells are elevated in the peripheral blood of breast cancer patients, but do not correlate with cancer stages. Nevertheless, the frequency of CD25 Tr1 cells was associated with nodal involvement, while the number of EM nTregs correlated with clinical outcome. The expression of CTLA-4 and IL-35 by all assessed Treg subsets was increased throughout all tumor stages (I-III).
Collectively, the current study shows phenotypic alterations in suppressive receptors of Treg subsets, suggesting that breast cancer patients have increased activity of N nTregs, EM nTregs and Tr1 cells; and EM nTregs and CD25 Tr1 cells represent prospective markers for assessing disease prognosis.
调节性 T 细胞（Tregs）通过抑制效应细胞在肿瘤逃避免疫监视中起主要作用。Tregs 的数量在肿瘤部位和乳腺癌患者的外周血中增加。然而，关于乳腺癌中 Treg 亚群的表型和功能异质性的数据有限。本研究旨在研究乳腺癌患者和健康女性中具有天然幼稚（N nTregs）、效应/记忆样（EM nTregs）和 Tr1 样表型的 Tregs 的数量和抑制潜能。
本研究包括 10 名 HW 和 17 名原发性乳腺癌患者。通过流式细胞术，在新鲜外周血中测量 CD4CD25FoxP3CD45RA N nTregs、CD4CD25FoxP3CD45RA EM nTregs 和 CD4IL-4IL-10 Tr1 亚群的数量，以及这些 Treg 亚群的 CTLA-4、CD39、GITR、LAP 和 IL-35 的表达。
在此，我们证明 N nTregs、EM nTregs、CD25 和 FoxP3 Tr1 细胞的百分比在乳腺癌患者的外周血中升高，但与癌症分期无关。然而，CD25 Tr1 细胞的频率与淋巴结受累有关，而 EM nTregs 的数量与临床结果相关。所有评估的 Treg 亚群的 CTLA-4 和 IL-35 表达均在所有肿瘤分期（I-III）中增加。
总的来说，本研究显示 Treg 亚群抑制性受体的表型改变，表明乳腺癌患者具有增加的 N nTregs、EM nTregs 和 Tr1 细胞活性；EM nTregs 和 CD25 Tr1 细胞是评估疾病预后的有前途的标志物。
