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卵巢癌免疫细胞谱分析识别出与不良临床特征和生存时间相关的免疫抑制状态

英文原题:Analysis of ovarian cancer immune cell profile identifies immunosuppressive states associated with adverse clinical attributes and survival times.

查看英文原题

Analysis of ovarian cancer immune cell profile identifies immunosuppressive states associated with adverse clinical attributes and survival times.

PubMed 2026/04/20(内容时间) PLoS One Q2 · IF 2.8(JCR 2025)

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中文摘要

卵巢肿瘤微环境(TME)具有高度免疫抑制性,限制了免疫治疗的效果。我们研究了浸润免疫细胞的组成、比例和极化是否对卵巢癌(OC)具有预后价值。

我们的分析显示,免疫比例,包括CD8/Treg和CD8/CD4,比绝对CD8+、CD4+或Treg水平更能预测生存。既往研究报道,较高的CD8/Treg比例与免疫检查点抑制剂应答改善相关,突显了效应-调节平衡的重要性;然而,本队列未评估免疫治疗应答。

此外,巨噬细胞极化被证明至关重要:促肿瘤M2巨噬细胞与血管侵犯、持续性肿瘤和更差生存相关,而较高的初始M0巨噬细胞水平预测结局改善。令人惊讶的是,抗肿瘤M1巨噬细胞缺乏预后意义,提示保留M0巨噬细胞池可能有益。中性粒细胞浸润虽然相对不常见,但与不良生存相关,支持中性粒细胞抑制T细胞应答的报道。免疫浸润与血管侵犯等侵袭性特征相关,反映了识别增强和抑制性细胞群代偿性募集。无监督聚类识别出四种免疫定义的亚型,其中富含M2巨噬细胞和CD4+ T细胞且M0巨噬细胞耗竭的聚类生存更差,尤其是在晚期疾病中。

总体而言,我们的发现突显了免疫比例、巨噬细胞极化和中性粒细胞活性在OC中的预后价值,提示了风险分层和未来治疗研究的新途径。

展开英文摘要原文

The ovarian tumor microenvironment (TME) is highly immunosuppressive, limiting immunotherapy effectiveness.

We investigated whether the composition, ratios, and polarization of infiltrating immune cells provide prognostic value in ovarian cancer (OC).

Our analysis revealed that immune ratios, including CD8/Treg and CD8/CD4, were more predictive of survival than absolute CD8 + , CD4 + , or Treg levels. Prior studies have reported associations between higher CD8/Treg ratios and improved responses to immune checkpoint inhibitors, highlighting the importance of effector-regulator balance; however, immunotherapy response was not evaluated in this cohort.

Additionally, macrophage polarization proved to be crucial: pro-tumor M2-macrophages were associated with vascular invasion, persistent tumor, and worse survival, while higher naïve M0-macrophage levels predicted improved outcomes. Surprisingly, anti-tumor M1-macrophages lacked prognostic significance, suggesting possible benefits in preserving an M0-macrophage pool. Neutrophil infiltration, though relatively uncommon, correlated with poor survival, supporting reports that neutrophils suppress T-cell responses.

Immune infiltration was linked to aggressive features such as vascular invasion, reflecting both heightened recognition and compensatory recruitment of suppressive populations. Unsupervised clustering identified four immune-defined subtypes, with worse survival in clusters enriched for M2-macrophages and CD4 + T-cells and depleted in M0-macrophages, particularly in advanced disease.

Overall, our findings highlight the prognostic value of immune ratios, macrophage polarization, and neutrophil activity in OC, suggesting new avenues for risk stratification and future therapeutic investigation.

论文信息

作者
Moscoso A、Mohammad Mirzaei N、Shahriyari L
单位
Department of Mathematics and Statistics, University of Massachusetts Amherst, Amherst, Massachusetts, United States of America.United States
期刊
PloS one2026
原文标识
PubMed 42008432 · DOI 10.1371/journal.pone.0346746