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乳腺癌引流淋巴结中 PD-1/PD-Ls 的表达及其预后意义

英文原题:Expression and Prognostic Significance of PD-1/PD-Ls in Breast Cancer Draining Lymph Nodes.

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Expression and Prognostic Significance of PD-1/PD-Ls in Breast Cancer Draining Lymph Nodes.

PubMed 2025/12/15(内容时间) Iran J Immunol Q4 · IF 1.1(JCR 2025)

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研究概要

BC 引流淋巴结中 PD-1 及其配体的表达升高与不良临床特征相关,提示其在免疫逃逸中的作用。这些发现以及三阴性患者中 PD-1+淋巴细胞频率较高,可能为亚型特异性治疗策略提供依据,并预测对 PD-1/PD-Ls 阻断疗法的反应性。未来研究应包括功能分析及更广泛的免疫表型分析,以进一步阐明这些机制。

研究思路结论见上方概要

肿瘤引流淋巴结在协调免疫细胞运输和启动抗肿瘤反应中发挥关键作用。在免疫调节分子中,程序性细胞死亡蛋白1(PD-1)已成为肿瘤诱导的免疫抑制中的核心介质。

探讨PD-1及其配体(PD-L1、PD-L2)在乳腺癌(BC)患者肿瘤引流淋巴结中的表达模式。

淋巴结样本从接受手术的BC患者中新鲜采集。分离单核细胞,并通过流式细胞术分析表面标志物CD45、PD-1、PD-L1和PD-L2。数据使用FlowJo v10.8.1进行分析。

在CD45+细胞中检测到PD-1的表达率为9.48 ± 5.19%,而PD-L1和PD-L2的表达水平较低(分别为1.73 ± 0.85%和1.68 ± 0.84%)。尽管CD45+淋巴细胞百分比显著降低,但在低分化和晚期肿瘤患者中,PD-1+和PD-L2+亚群的频率显著升高(P<0.05)。此外,在三阴性肿瘤患者(P=0.014)以及雌激素和孕激素受体阴性患者(P=0.001)中,PD-1+淋巴细胞的频率显著更高。

展开英文摘要原文

Tumor-draining lymph nodes play a pivotal role in orchestrating immune cell trafficking and initiating antitumor responses. Among immunoregulatory molecules, programmed cell death protein 1 (PD-1) has emerged as a central mediator in tumor-induced immunosuppression.

To investigate the expression patterns of PD-1 and its ligands (PD-L1, PD-L2) in the tumor-draining lymph nodes of patients with breast cancer (BC).

Lymph node samples were freshly collected from BC patients undergoing surgery. Mononuclear cells were isolated and analyzed by flow cytometry for surface markers CD45, PD-1, PD-L1, and PD-L2. Data were analyzed using FlowJo v10.8.1.

PD-1 was detected on 9.48 ± 5.19% of CD45+ cells, whereas PD-L1 and PD-L2 were expressed at lower levels (1.73 ± 0.85% and 1.68 ± 0.84%, respectively). Despite a significant reduction in the percentage of CD45+ lymphocytes, the frequencies of PD-1+ and PD-L2+ subsets were significantly elevated in patients with poorly-differentiated and advanced-stage tumors (P<0.05). Additionally, the frequency of PD-1+ lymphocytes was significantly higher in patients with the triple-negative tumors (P=0.014) and in those negative for estrogen and progesterone receptor (P=0.001).

Elevated expression of PD-1 and its ligands in BC-draining lymph nodes is associated with adverse clinical features, suggesting their role in immune evasion. These findings along with higher frequency of PD-1+ lymphocyte in triple-negative patients may inform subtype-specific therapeutic strategies and predict responsiveness to PD-1/PD-Ls blockade therapies. Future studies should include functional analyses with broader immunophenotyping to further elucidate these mechanisms.

论文信息

作者
Mansourabadi Z、Moazzeni A、Akrami M、Fakhimi M、Faghih Z
第一作者单位
Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.Iran
通讯作者单位
Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.Iran
期刊
Iranian journal of immunology : IJI2025 Dec 15
原文标识
PubMed 41394074 · DOI 10.22034/iji.2025.107984.3084