免疫抑制 MDSC 和 Treg 特征可预测神经胶质瘤的预后和治疗反应。
Immunosuppressive MDSC and Treg signatures predict prognosis and therapeutic response in glioma.
发表日期:2024 Aug 12
作者:
Bowen Yin, Yiheng Cai, Lingxia Chen, Zhenyu Li, Xiaofei Li
来源:
INTERNATIONAL IMMUNOPHARMACOLOGY
摘要:
神经胶质瘤是一种复杂且具有侵袭性的脑肿瘤,其特点是肿瘤微环境 (TME) 内的免疫反应失调。我们进行了全面分析,以阐明髓源性抑制细胞 (MDSC) 和调节性 T 细胞 (Treg) 在神经胶质瘤进展中的作用及其对免疫环境的影响。使用转录组数据,我们根据 MDSC 和 Treg 水平对神经胶质瘤样本进行分层,揭示了患者生存概率的显着差异。 LASSO 回归确定了与神经胶质瘤预后相关的基因组,从而产生患者特定的风险评分。多变量 Cox 回归证实了风险评分与总生存期的相关性。 ISS(免疫抑制评分)系统评估了免疫环境对神经胶质瘤进展和治疗反应的影响。功能验证表明 MDSC 和 Treg 浸润与神经胶质瘤进展和免疫调节相关。通过MCODE分析鉴定出黑色模块中的Hub基因,包括CCL2、LINC01503、CXCL8、CLEC2B、TIMP1和RGS2。 RGS2 表达与免疫细胞群相关,并且在神经胶质瘤细胞中存在差异。这项研究揭示了 MDSC 和 Tregs 在神经胶质瘤发病机制中的作用,表明它们作为神经胶质瘤治疗中个性化免疫治疗策略的预后生物标志物和治疗靶标的潜力。版权所有 © 2024。由 Elsevier B.V. 出版。
Glioma, a complex and aggressive brain tumor, is characterized by dysregulated immune responses within the tumor microenvironment (TME). We conducted a comprehensive analysis to elucidate the roles of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) in glioma progression and their impact on the immune landscape. Using transcriptome data, we stratified glioma samples based on MDSC and Treg levels, revealing significant differences in patient survival probabilities. LASSO regression identified a gene panel associated with glioma prognosis, yielding a patient-specific risk score. Multivariate Cox regression confirmed the risk score's correlation with overall survival. An ISS (immune suppressive score) system assessed the immune landscape's impact on glioma progression and therapeutic response. Functional validation showed MDSC and Treg infiltration's relevance in glioma progression and immune modulation. Hub genes in the black module, including CCL2, LINC01503, CXCL8, CLEC2B, TIMP1, and RGS2, were identified through MCODE analysis. RGS2 expression correlated with immune cell populations and varied in glioma cells. This study sheds light on MDSCs' and Tregs' roles in glioma pathogenesis, suggesting their potential as prognostic biomarkers and therapeutic targets for personalized immunotherapeutic strategies in glioma treatment.Copyright © 2024. Published by Elsevier B.V.