研究动态
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膀胱癌患者肿瘤引流淋巴结中记忆 CD8 T 细胞的多样性。

Diversity of Memory CD8+ T Cells in Tumor-Draining Lymph Nodes from Patients with Bladder Cancer.

发表日期:2024
作者: Ali Ariafar, Zahra Mansourabadi, Shahin Rasekh, Maryam Fakhimi, Zahra Faghih
来源: Stem Cell Research & Therapy

摘要:

记忆 T 细胞在协调对先前已知肿瘤抗原的记忆反应中的作用已有充分记录。本研究的目的是评估膀胱癌 (BC) 患者肿瘤引流淋巴结中不同记忆 T 细胞亚群的频率及其预后意义。从未经治疗的 BC 患者的 50 个肿瘤引流淋巴结中分离出单核细胞,并用针对标记物 CD8、CD95、CD45RO 和 CCR7 的抗体进行染色。使用 FACSCalibur 流式细胞仪收集数据并使用 FlowJo 软件进行分析。在CD8细胞毒性淋巴细胞中,确定了不同亚群的频率,包括总记忆细胞(CD8 CD45RO CD95 )、T中央记忆(TCM:CD8 CCR7 CD45RO CD95 )、T效应记忆(TEM:CD8 CCR7-CD45RO CD95 )、T干细胞细胞记忆(TSCM:CD8 CCR7 CD45RO-CD95)和幼稚 T 细胞(CD8 CCR7 CD45RO-CD95-)。分析显示,BC 引流淋巴结中平均 49.32±20.15%(1.62% 至 87.20%)的 CD8 淋巴细胞具有记忆表型。 TCM细胞的频率最高(34.71±17.04),而TSCM细胞的频率最低(7.51±8.53)。肿瘤侵犯肌层(P=0.052)和Ⅲ期患者(P=0.042)记忆细胞总频率高于无侵犯和Ⅰ期患者。TCM亚群在坏死性肿瘤患者中出现频率更高。肿瘤的发生率高于无坏死的患者(P=0.048)。与 N0 患者相比,N2 患者的 TSCM 显着增加(P=0.042)。相反,低肿瘤分期(P=0.059)、无肌肉侵犯的肿瘤(P=0.026)和低T组(P=0.043)中TSCM细胞占总记忆细胞的比例较高。总体而言,数据表明随着肿瘤进展,记忆 T 细胞及其 TSCM 和 TCM 细胞的频率增加。相反,在较不晚期的肿瘤中,TSCM 与总记忆细胞的比例较高。这些结果表明,免疫系统经常暴露于肿瘤抗原并努力创建记忆T细胞库,但这会受到肿瘤提供的抑制因子的抑制。这些发现强调了理解记忆 T 细胞亚群与 BC 进展之间动态相互作用的重要性。© 作者。
The role of memory T cells in orchestrating memory responses to previously known tumor antigens is well documented. The aim of this study was to assess the frequency of different memory T cell subsets in tumor-draining lymph nodes of patients with bladder cancer (BC) and their prognostic significance. Mononuclear cells were isolated from 50 tumor-draining lymph nodes of untreated patients with BC and stained with antibodies against the markers CD8, CD95, CD45RO and CCR7. Data were collected using the FACSCalibur flow cytometer and analyzed using FlowJo software. Among the CD8+ cytotoxic lymphocytes, the frequency of different subsets was determined including total memory cells (CD8+CD45RO+CD95+), T central memory (TCM: CD8+CCR7+CD45RO+CD95+), T effector memory (TEM: CD8+CCR7-CD45RO+CD95+), T stem cell memory (TSCM: CD8+CCR7+CD45RO-CD95+) and naïve T cells (CD8+CCR7+CD45RO-CD95-). The analysis revealed that on average 49.32±20.15 (between 1.62% and 87.20%) percent of CD8+ lymphocytes in draining lymph nodes of BC had a memory phenotype. TCM cells showed the highest frequency (34.71±17.04), while TSCM cells (7.51±8.53) demonstrated the lowest. The total frequency of memory cells tended to be higher in patients with tumor invasion to muscle layer (P=0.052) and stage III (P=0.042) than in patients without invasion and stage I. The TCM subset was more frequent in patients with necrotic tumors than in patients without necrosis (P=0.048). TSCM significantly increased in patients with N2 compared to N0 (P=0.042). Conversely, the ratio of TSCM cells to total memory cells was higher in lower tumor stages (P=0.059), tumors without muscle invasion (P=0.026) and low T grouping (P=0.043). Overall the data indicated an increase in the frequency of memory T cells and their TSCM and TCM cells with tumor progression. In contrast, the ratio of TSCM to total memory cells was higher in less advanced tumors. These results suggest that the immune system is frequently exposed to tumor antigens and strives to create a memory T cell reservoir, but this is suppressed by inhibitory factors provided by the tumor. These findings emphasize the importance of understanding the dynamic interplay between memory T cell subsets and BC progression.© The Author(s).