Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, P.O. Box: 71345-1798, Shiraz, Iran.
Department of Pathology, Shiraz Central Hospital, Shiraz, Iran.
BMC Cancer. 2020 Mar 30;20(1):257. doi: 10.1186/s12885-020-6714-x.
Human immunological memory is a hallmark of the adaptive immune system and plays an important role in the development of effective immune responses against tumors. In the present study, we aimed to determine the frequencies of CD8 memory T cell subsets including T stem cell memory (TSCM) in tumor-draining lymph nodes of patients with breast cancer (BC).
Mononuclear cells were obtained from axillary lymph nodes of 52 untreated patients with BC and stained for CD8, CCR7, CD45RO, CD95 markers to detect different subtypes of memory cells in the CD8 lymphocyte population. Data were acquired on four-color flow cytometer and analyzed with CellQuest Pro software.
We observed that 47.65 ± 2.66% of CD8 lymphocytes expressed the CD45RO, a marker for memory T cells. Statistical analysis showed that the total frequency of central memory T cells (TCM) and their subset with low CD45RO expression was significantly higher in tumor-involved nodes compared to tumor-free ones (P = 0.024 and P = 0.017, respectively). The level of CD95 expression (based on mean fluorescence intensity) on the surface of TCM, their CD45RO and CD45RO subsets, and TSCM was higher in patients with stage II compared to those in stage I (P < 0.05). In addition, the percentage of naive CD8 T cells was significantly lower in tumor-involved lymph nodes compared to tumor-free ones (P = 0.025).
Our data collectively indicate no significant differences in the frequencies of CD8 lymphocytes or their memory subsets in tumor-draining lymph nodes of patients with BC. However, the frequency of CD45 TCM was higher in tumor-involved nodes. Along with a decrease in the frequency of naive T cells, the higher frequency of CD45 TCM suggests that despite the immune reaction to provide a pool of effective memory cells, it is blocked in early-stage of memory cells' differentiation (CD45RO), probably by tumor-derived suppressive factors. Identifying the molecular and cellular mechanisms behind this suppression can provide invaluable tools for adoptive T cell therapies in cancer.
人类免疫记忆是适应性免疫系统的一个标志，在针对肿瘤产生有效免疫反应中发挥重要作用。在本研究中，我们旨在确定乳腺癌（BC）患者肿瘤引流淋巴结中 CD8 记忆 T 细胞亚群（包括 T 干细胞记忆（TSCM））的频率。
从 52 例未经治疗的 BC 患者的腋窝淋巴结中获得单核细胞，并对其进行 CD8、CCR7、CD45RO、CD95 标志物染色，以检测 CD8 淋巴细胞群中不同记忆细胞亚群。数据通过四色流式细胞仪采集，并使用 CellQuest Pro 软件进行分析。
我们发现，47.65±2.66%的 CD8 淋巴细胞表达 CD45RO，这是记忆 T 细胞的标志物。统计分析表明，与无肿瘤淋巴结相比，肿瘤受累淋巴结中总中央记忆 T 细胞（TCM）及其低 CD45RO 表达亚群的频率显著更高（P=0.024 和 P=0.017）。与 I 期患者相比，Ⅱ期患者 TCM 及其 CD45RO 和 CD45RO 亚群以及 TSCM 表面 CD95 表达（基于平均荧光强度）水平更高（P<0.05）。此外，与无肿瘤淋巴结相比，肿瘤受累淋巴结中幼稚 CD8 T 细胞的百分比显著更低（P=0.025）。
我们的数据共同表明，BC 患者肿瘤引流淋巴结中 CD8 淋巴细胞或其记忆亚群的频率没有显著差异。然而，肿瘤受累淋巴结中 CD45 TCM 的频率更高。随着幼稚 T 细胞频率的降低，CD45 TCM 的更高频率表明，尽管免疫反应提供了有效的记忆细胞池，但它被阻断在记忆细胞分化的早期（CD45RO），可能是由肿瘤衍生的抑制因子引起的。鉴定这种抑制背后的分子和细胞机制可以为癌症的过继性 T 细胞治疗提供宝贵的工具。
