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胶质母细胞瘤中PD-L1和CD45RO细胞的预后意义:错配修复状态的调节作用

Prognostic significance of PD-L1 and CD45RO cells in glioblastoma: The modulating role of MMR status.

作者信息

Mohammadi Yousef, Kaviani Elina, Ahmadvand Simin, Dehghanian Amirreza, Ghaderi Abbas

机构信息

Shiraz Institute for Cancer Research, 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; Cancer Prevention Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

出版信息

J Neuroimmunol. 2025 Sep 15;406:578669. doi: 10.1016/j.jneuroim.2025.578669. Epub 2025 Jun 15.

Abstract

BACKGROUND

Glioblastoma (GBM) is the most prevalent and aggressive primary malignant brain tumor with limited treatment options and poor prognosis. Prognostic biomarkers, including immune checkpoint molecules and tumor-infiltrating lymphocytes, offer valuable insights into disease outcomes and potential therapeutic targets. This study uses Immunohistochemical analyses to explore the roles of PD-L1, CD45RO cells, and other key biomarkers in GBM prognosis.

METHODS

Immunohistochemical (IHC) staining of PD-1, PD-L1, CD45RO, mismatch repair (MMR) proteins, and Ki-67 was conducted on 63 formalin-fixed paraffin-embedded (FFPE) GBM tissue samples. Statistical analyses, including Cox regression, assessed the prognostic impact of these biomarkers.

RESULTS

IHC staining results indicated limited immune infiltration in the tumor tissue. High PD-L1 expression (HR: 1.926) and elevated CD45RO cells infiltration (HR: 2.122) were significantly associated with reduced OS in GBM patients. Subgroup analyses revealed that PD-L1 and CD45RO cells had a stronger prognostic impact in MMR-proficient patients, whereas IDH mutation status remained the only independent prognostic marker in MMR-deficient GBM cases.

CONCLUSIONS

PD-L1 and CD45RO cells serve as key prognostic biomarkers in GBM, particularly in MMR-proficient patients. These findings underscore the potential for personalized immunotherapies targeting immune checkpoint pathways to improve GBM outcomes. Further research is warranted to explore the therapeutic implications of these markers in GBM subgroups.

摘要

背景

胶质母细胞瘤(GBM)是最常见且侵袭性最强的原发性恶性脑肿瘤,治疗选择有限且预后较差。包括免疫检查点分子和肿瘤浸润淋巴细胞在内的预后生物标志物,为疾病结局和潜在治疗靶点提供了有价值的见解。本研究采用免疫组织化学分析方法,探讨程序性死亡配体1(PD-L1)、CD45RO细胞及其他关键生物标志物在GBM预后中的作用。

方法

对63例福尔马林固定石蜡包埋(FFPE)的GBM组织样本进行PD-1、PD-L1、CD45RO、错配修复(MMR)蛋白和Ki-67的免疫组织化学(IHC)染色。包括Cox回归分析在内的统计分析评估了这些生物标志物的预后影响。

结果

IHC染色结果表明肿瘤组织中免疫浸润有限。GBM患者中,高PD-L1表达(风险比:1.926)和CD45RO细胞浸润增加(风险比:2.122)与总生存期缩短显著相关。亚组分析显示,PD-L1和CD45RO细胞在MMR功能正常的患者中具有更强的预后影响,而在MMR缺陷的GBM病例中,异柠檬酸脱氢酶(IDH)突变状态仍然是唯一的独立预后标志物。

结论

PD-L1和CD45RO细胞是GBM的关键预后生物标志物,尤其是在MMR功能正常的患者中。这些发现强调了针对免疫检查点通路的个性化免疫疗法改善GBM结局的潜力。有必要进一步研究探索这些标志物在GBM亚组中的治疗意义。

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