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静息肥大细胞的转录特征与 HR(+)HER2(-) 乳腺癌疾病结局改善相关

英文原题:A transcriptional signature of resting mast cells is associated with improved disease outcome in HR(+)HER2(-) breast cancer.

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A transcriptional signature of resting mast cells is associated with improved disease outcome in HR(+)HER2(-) breast cancer.

PubMed 2026/07/31(内容时间) Genes Immun Q1 · IF 4.2(JCR 2025)

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中文摘要

乳腺癌是全球女性中最常见的恶性肿瘤,每年导致超过650,000例死亡。尽管个性化治疗取得了进展,但许多患者未能从针对其疾病亚型的治疗中获得持久获益。例如,只有部分PD-L1⁺三阴性乳腺癌(TNBC)患者对化疗联合免疫检查点抑制剂有应答。

此外,虽然TIL(肿瘤浸润淋巴细胞)水平与TNBC和HER2⁺乳腺癌的生存改善相关,但在HR⁺HER2-疾病中并非如此。

因此,乳腺癌微环境的其他免疫生物学特征可能具有临床相关的预后或预测价值,尤其是在HR⁺HER2-肿瘤中。在此,我们研究了三个公开乳腺癌患者转录组数据集中免疫细胞浸润的转录特征。肿瘤浸润肥大细胞的相对丰度和活化状态始终与HR⁺HER2-乳腺癌患者生存指标的变化相关。

具体而言,静息(而非活化)肥大细胞的浸润与生存延长相关,与免疫细胞浸润和癌细胞增殖标志物呈负相关,但与基质丰富度呈正相关。虽然基于回顾性转录分析,这些发现提示肥大细胞与乳腺癌微环境中非恶性成分(尤其是成纤维细胞)之间的相互作用可能影响疾病进展和治疗敏感性。

展开英文摘要原文

Breast cancer is the most common malignancy among women worldwide, causing >650,000 deaths annually. Despite advances in personalized therapies, many patients fail to obtain durable benefits from treatments tailored to their disease subtype. For instance, only some patients with PD-L1⁺ triple-negative breast cancer (TNBC) respond to chemotherapy plus immune checkpoint inhibitors.

Moreover, while tumor-infiltrating lymphocyte levels correlate with improved survival in TNBC and HER2⁺ breast cancer, this is not true for HR⁺HER2 - disease.

Thus, other immunobiological features of the breast cancer microenvironment may hold clinically relevant prognostic or predictive value, especially in HR + HER2 - tumors.

Here, we investigated transcriptional signatures of immune cell infiltration across three public transcriptomic datasets from patients with breast cancer. The relative abundance and activation status of tumor-infiltrating mast cells were consistently associated with shifts in survival indicators amongst patients with HR + HER2 - breast cancer.

Specifically, infiltration by resting (but not activated) mast cells was associated with prolonged survival, correlating inversely with tumor infiltration by immune cells and proliferation markers in cancer cells, but positively with stromal richness. While based on retrospective transcriptional analyses, these findings suggest that interactions between mast cells and non-malignant components of the breast cancer microenvironment, particularly fibroblasts, may shape disease progression and treatment sensitivity.

论文信息

作者
Kirchmair A、Galassi C、García-Torralba E、Trajanoski Z、Buqué A、Galluzzi L
第一作者单位
Biocenter, Institute of Bioinformatics, Medical University of Innsbruck, Innsbruck, Austria.Austria
通讯作者单位
Cancer Signaling and Microenvironment Program, Fox Chase Cancer Center, Philadelphia, PA, USA. deadoc80@gmail.com.United States
期刊
Genes and immunity2026 Jul 31
原文标识
PubMed 42538366 · DOI 10.1038/s41435-026-00409-y