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
三阴性乳腺癌中半乳糖凝集素与免疫关联的整合多组学及单细胞分析
英文原题：Integrated multi-omics and single-cell analysis of galectins and immune associations in triple-negative breast cancer.
查看英文原题
Integrated multi-omics and single-cell analysis of galectins and immune associations in triple-negative breast cancer.
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研究思路按摘要原文分段
背景
三阴性乳腺癌（TNBC）是一种缺乏有效靶向治疗的侵袭性亚型。半乳糖凝集素（Galectins）是一类β-半乳糖苷结合凝集素家族，已成为肿瘤-免疫相互作用的重要介质，但其在TNBC肿瘤微环境中的细胞类型特异性表达模式及功能作用仍不明确。
方法
我们将FUSCC（n = 465）和TCGA（n = 161）TNBC队列的批量转录组和基因组数据与26例未接受治疗患者的单细胞RNA测序数据进行了整合。我们系统评估了galectin表达、基因组改变、预后意义、与免疫检查点和免疫浸润的关联，以及与免疫背景和治疗反应相关的细胞类型特异性模式。
结果
Galectin家族成员在TNBC中表现出广泛失调，反复出现的拷贝数改变导致了转录异质性。在bulk水平上，LGALS2与有利生存相关，而LGALS3预示不良预后。包括LGALS2、LGALS9和LGALS10在内的几种galectin与免疫检查点表达呈正相关，并富集免疫浸润，尤其涉及CD8⁺ T细胞和TIL（肿瘤浸润淋巴细胞）。单细胞分析揭示了恶性、免疫和基质区室中不同的galectin表达，提示转录组推断的免疫背景具有异质性。Galectin表达也因治疗反应而异：新辅助化疗-免疫治疗的病理完全缓解（pCR）与较高的LGALS3和较低的LGALS2、LGALS8和LGALS9相关，而化疗的pCR与较高的LGALS9和较低的LGALS1相关。
结论
我们的研究全面描述了TNBC中半乳糖凝集素家族成员的特征，揭示了它们的预后意义以及与肿瘤微环境和治疗反应的关联，并强调了半乳糖凝集素作为候选生物标志物和未来机制研究的假设生成分子的临床和转化相关性。
展开英文摘要原文
BACKGROUND
Triple-negative breast cancer (TNBC) is an aggressive subtype lacking effective targeted therapies. Galectins, a family of β-galactoside-binding lectins, have emerged as important mediators of tumor-immune interactions, but their cell-type-specific expression patterns and functional roles within the tumor microenvironment of TNBC remain poorly defined.
METHODS
We integrated bulk transcriptomic and genomic data from FUSCC (n = 465) and TCGA (n = 161) TNBC cohorts with single-cell RNA sequencing data from 26 treatment-naïve patients. We systematically assessed galectin expression, genomic alterations, prognostic significance, associations with immune checkpoints and immune infiltration, and cell-type-specific patterns linked to immune contexts and therapeutic response.
RESULTS
Galectin family members showed broad dysregulation in TNBC, with recurrent copy number alterations contributing to transcriptional heterogeneity. At the bulk level, LGALS2 was associated with favorable survival, while LGALS3 predicted poor prognosis. Several galectins, including LGALS2, LGALS9, and LGALS10, exhibited positive correlations with immune checkpoint expression and enriched immune infiltration, particularly involving CD8⁺ T cells and tumor-infiltrating lymphocytes. Single-cell analysis revealed distinct galectin expression across malignant, immune, and stromal compartments, suggesting heterogeneous transcriptomically inferred immune contexts. Galectin expression also differed by treatment response: pathological complete response (pCR) to neoadjuvant chemo-immunotherapy was associated with higher LGALS3 and lower LGALS2, LGALS8, and LGALS9, while pCR to chemotherapy was linked to higher LGALS9 and lower LGALS1.
CONCLUSIONS
Our study comprehensively characterizes galectin family members in TNBC, revealing their prognostic significance and association with tumor microenvironment and treatment response, and highlighting the clinical and translational relevance of galectins as candidate biomarkers and hypothesis-generating molecules for future mechanistic studies.
论文信息
- 作者
- Ji P、Liu H、Di GH、Shao ZM、Gong Y
- 第一作者单位
- Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.China
- 通讯作者单位
- Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. Electronic address: yuegong@fudan.edu.cn.China
- 期刊
- Translational oncology2026 Sep
- 原文标识
- PubMed 42391674 · DOI 10.1016/j.tranon.2026.102887
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