Ariafar Ali, Mansourabadi Zahra, Rasekh Shahin, Fakhimi Maryam, Faghih Zahra
Department of Urology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Int J Mol Cell Med. 2024;13(2):147-159. doi: 10.22088/IJMCM.BUMS.13.2.147.
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 (CD8CD45ROCD95), T central memory (TCM: CD8CCR7CD45ROCD95), T effector memory (TEM: CD8CCR7CD45ROCD95), T stem cell memory (TSCM: CD8CCR7CD45ROCD95) and naïve T cells (CD8CCR7CD45ROCD95). 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.
记忆T细胞在协调针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个引流淋巴结中分离出单核细胞，并用抗CD8、CD95、CD45RO和CCR7标志物的抗体进行染色。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（CD8CD45ROCD95）、中央记忆T细胞（TCM：CD8CCR7CD45ROCD95）、效应记忆T细胞（TEM：CD8CCR7CD45ROCD95）、干细胞记忆T细胞（TSCM：CD8CCR7CD45ROCD95）和初始T细胞（CD8CCR7CD45ROCD95）。分析显示，BC引流淋巴结中平均49.32±20.15（1.62%至87.20%之间）的CD8淋巴细胞具有记忆表型。TCM细胞频率最高（34.71±17.04），而TSCM细胞（7.51±8.53）频率最低。肿瘤侵犯肌层的患者（P = 0.052）和III期患者（P = 0.042）的记忆细胞总频率往往高于无侵犯和I期患者。坏死肿瘤患者的TCM亚群比无坏死患者更常见（P = 0.048）。与N0患者相比，N2患者的TSCM显著增加（P = 0.042）。相反，在较低肿瘤分期（P = 0.059）、无肌层侵犯的肿瘤（P = 0.026）和低T分组（P = 0.043）中，TSCM细胞与总记忆细胞的比例更高。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。相比之下，在进展较慢的肿瘤中，TSCM与总记忆细胞的比例更高。这些结果表明，免疫系统经常暴露于肿瘤抗原，并努力建立记忆T细胞库，但这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。
