基于 DNA 超分子水凝胶的保护性 NK 细胞储库用于增强三阴性乳腺癌治疗
Protective NK Cell Reservoir Based on DNA Supramolecular Hydrogel for Enhanced Triple-Negative Breast Cancer Therapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
空间蛋白质组学分析揭示局部晚期三阴性乳腺癌中 NF1-Ras/Raf/MEK 信号与免疫细胞浸润之间的关联
英文原题：Spatial proteomic profiling reveals an association between NF1-Ras/Raf/MEK signaling and immune cell infiltration in locally advanced triple-negative breast cancer.
查看英文原题
Spatial proteomic profiling reveals an association between NF1-Ras/Raf/MEK signaling and immune cell infiltration in locally advanced triple-negative breast cancer.
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研究概要
这些发现推进了我们对 TNBC 空间蛋白质组谱的理解，并提示靶向 NF1-Ras/Raf/MEK 轴可能为免疫“热”肿瘤 TNBC 患者的临床管理提供新策略。
研究思路结论见上方概要
背景
三阴性乳腺癌（TNBC）是一种高度侵袭性的恶性肿瘤，具有显著的分子异质性，靶向治疗选择有限。更好地解析肿瘤细胞与免疫微环境之间的空间相互作用，对于识别可干预的脆弱靶点至关重要。
方法
我们采用GeoMx数字空间图谱分析（DSP）技术，对29例初治TNBC患者（接受前期乳房手术）的正常乳腺、原发乳腺癌及转移性腋窝淋巴结组织中的72种免疫肿瘤生物标志物进行了蛋白质组学景观研究。
结果
通过全面的蛋白质组学分析，我们确定了肿瘤抑制蛋白神经纤维瘤蛋白（NF1）是 TNBC 的脆弱性之一。空间分辨分析显示，NF1 下调与 Ras/Raf/MEK 通路激活密切相关。NF1 水平的这种下调是TIL（肿瘤浸润淋巴细胞）（TILs）高度代表的肿瘤区域的特征。此外，低 NF1 水平与无病生存期缩短显著相关，表明其作为生物标志物的潜在临床效用。我们还观察到原发性乳腺肿瘤与匹配的淋巴结转移之间具有高度的蛋白质组相似性。
展开英文摘要原文
BACKGROUND
Triple-negative breast cancer (TNBC) is a highly aggressive malignancy characterized by significant molecular heterogeneity with a limited range of targeted therapy options. Better resolution of the spatial interactions between tumor cells and the immune microenvironment is essential for identifying actionable vulnerabilities.
METHODS
Here we employed GeoMx Digital Spatial Profiling (DSP) to investigate the proteomic landscape of 72 immuno-oncology biomarkers in normal breast, primary breast cancer, and metastatic axillary lymph node tissues of treatment-naïve TNBC patients (n=29) who underwent upfront breast surgery.
RESULTS
Through comprehensive profiling, we identified the tumor suppressor protein, neurofibromin (NF1), as one of the vulnerabilities in TNBC. Spatially resolved analysis revealed that NF1 downregulation is strongly associated with Ras/Raf/MEK pathway activation. This downregulation of NF1 level was characteristic of tumor regions with a high representation of tumor infiltrating lymphocytes (TILs). Furthermore, low NF1 levels significantly correlated with reduced disease-free survival, suggesting its potential clinical utility as a biomarker. We also observed a high degree of proteomic similarity between primary breast tumors and the matched lymph node metastases.
CONCLUSIONS
These findings advance our understanding of TNBC spatial proteomic profiles and suggest that targeting the NF1-Ras/Raf/MEK axis may offer novel strategy for clinical management of TNBC patients with immune "hot" tumors.
论文信息
- 作者
- Bhat V、Goebel E、Postenka C、Santiago AFG、Wei Y、Brackstone M、Allan AL、Parsyan A
- 第一作者单位
- Department of Anatomy and Cell Biology, Schulich School of Medicine & Dentistry, Western University, London, ON, N6A 5C1, Canada; Department of Oncology, Schulich School of Medicine & Dentistry, Western University, London, ON, N6A 5W9, Canada; Verspeeten Family Cancer Centre, London Health Sciences Centre and London Health Sciences Centre Research Institute, London, ON, N6A 4L6, Canada. Electronic address: vbhat@uwo.ca.Canada
- 通讯作者单位
- Department of Anatomy and Cell Biology, Schulich School of Medicine & Dentistry, Western University, London, ON, N6A 5C1, Canada; Department of Oncology, Schulich School of Medicine & Dentistry, Western University, London, ON, N6A 5W9, Canada; Verspeeten Family Cancer Centre, London Health Sciences Centre and London Health Sciences Centre Research Institute, London, ON, N6A 4L6, Canada; St Joseph's Health Care London, ON, N6A 4V2, Canada; Department of Surgery, Schulich School of Medicine & Dentistry, London, ON, N6A 4V2, Canada. Electronic address: aparsyan@uwo.ca.Canada
- 期刊
- Translational oncology2026 Oct
- 原文标识
- PubMed 42520478 · DOI 10.1016/j.tranon.2026.102934
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