Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Cell Oncol (Dordr). 2018 Feb;41(1):1-11. doi: 10.1007/s13402-017-0352-6. Epub 2017 Oct 9.
The compartments of memory T cells play a fundamental role in the immune system by substantiating specific and acquired immunity. A new subset of memory cells, T stem cell memory (T) cells, with stem cell-like properties, a high capacity to proliferate, a long survival, and an ability to differentiate into all effector and memory cells has recently been introduced. In the present study, we aimed to determine the frequency of CD4 T and other T memory cell subsets in tumor draining lymph nodes of breast cancer patients.
Mononuclear cells were obtained from axillary lymph nodes of 52 untreated patients with breast cancer (BC) and stained with fluorochrome conjugated anti-CD4, -CCR7, -CD45RO and -CD95 antibodies to detect different subtypes of memory cells in CD4 lymphocyte populations. Data were acquired using a four-color FACSCalibur flow cytometer and analyzed using CellQuest Pro software.
We found that >70% of CD4 lymphocytes in draining lymph nodes of BC patients exhibited a memory phenotype of which 7.04 ± 1.04% had a T phenotype (CD4CCR7CD45ROCD95). The frequency of T cells was significantly higher in tumor positive lymph nodes compared to tumor negative lymph nodes (p = 0.026) as well as among those patients who had at least one affected lymph node (p = 0.012). Moreover, we found that the total frequency of central memory T cells (T) with a low expression of CD45RO was significantly higher among these patients. The percentage of CD45RO T cells was also found to increase with tumor progression from stage I to stage III (p = 0.020). On the other hand, we found that the percentage of CD95 effector memory T cells (T) was significantly decreased in involved lymph nodes (p = 0.009).
Our data suggest that following long-term exposure to putative tumor antigens, T cells proliferate to generate a pool of committed memory and effector T cells. As the tumor progresses, the immunosuppressive milieu induced by tumor cells may slow down the differentiation of CD45RO T cells to more functional sub-populations.
记忆 T 细胞的隔室在通过证实特定和获得性免疫来支撑特异性和获得性免疫方面发挥着根本性作用。最近引入了一种新的记忆细胞亚群，T 干细胞记忆（T）细胞，具有干细胞样特性、高增殖能力、长存活期和分化为所有效应和记忆细胞的能力。在本研究中，我们旨在确定乳腺癌患者肿瘤引流淋巴结中 CD4 T 细胞和其他 T 记忆细胞亚群的频率。
从 52 例未经治疗的乳腺癌（BC）患者的腋窝淋巴结中获得单核细胞，并使用荧光标记的抗 CD4、-CCR7、-CD45RO 和 -CD95 抗体对其进行染色，以检测 CD4 淋巴细胞群中不同的记忆细胞亚群。使用四色 FACSCalibur 流式细胞仪获取数据，并使用 CellQuest Pro 软件进行分析。
我们发现，BC 患者引流淋巴结中超过 70%的 CD4 淋巴细胞表现出记忆表型，其中 7.04±1.04%具有 T 表型（CD4CCR7CD45ROCD95）。与肿瘤阴性淋巴结相比，肿瘤阳性淋巴结中的 T 细胞频率明显更高（p=0.026），且在至少有一个受累淋巴结的患者中更高（p=0.012）。此外，我们发现这些患者中，低表达 CD45RO 的中央记忆 T 细胞（T）的总频率明显更高。CD45RO T 细胞的百分比也随着肿瘤从 I 期进展到 III 期而增加（p=0.020）。另一方面，我们发现，在受累淋巴结中，CD95 效应记忆 T 细胞（T）的百分比明显降低（p=0.009）。
我们的数据表明，在长期暴露于潜在的肿瘤抗原后，T 细胞增殖以产生一个有承诺的记忆和效应 T 细胞池。随着肿瘤的进展，肿瘤细胞诱导的免疫抑制环境可能会减缓 CD45RO T 细胞向更具功能的亚群分化。
