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
基于免疫组织化学的分子亚型与三阴性乳腺癌中的间质 TIL（肿瘤浸润淋巴细胞）：一项仅化疗队列研究
英文原题：Immunohistochemistry-based molecular subtypes and stromal tumor-infiltrating lymphocytes in triple-negative breast cancer: a chemotherapy-only cohort.
查看英文原题
Immunohistochemistry-based molecular subtypes and stromal tumor-infiltrating lymphocytes in triple-negative breast cancer: a chemotherapy-only cohort.
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研究概要
临床病理因素和 sTILs 仍是 TNBC 的主要预后决定因素。尽管基于 IHC 的分子亚型并非独立的生存预测因子，但其差异化的临床分布验证了其在识别治疗脆弱性、指导精准医学和降阶梯策略方面的生物学相关性。
研究思路结论见上方概要
背景
三阴性乳腺癌（TNBC）是一种生物学异质性、侵袭性疾病，基于免疫组化（IHC）的算法定义了管腔雄激素受体（LAR）、免疫调节（IM）、基底样免疫抑制（BLIS）、间充质（MES）和不可分类（UC）亚型，为转录组学提供了一种实用的替代方案。本研究评估了在不同亚组中，基于IHC的分子亚型与间质TIL（肿瘤浸润淋巴细胞）（sTILs）相关的临床轨迹和生存结局。
方法
一项对289例仅接受化疗方案治疗的TNBC女性患者的回顾性分析，在四个临床组别中分析了分子亚型：未复发、复发、新辅助化疗期间进展以及初诊转移性疾病。基于IHC的亚分类包括雄激素受体（AR）、CD8、FOXC1和DCLK1生物标志物。总生存期（OS）和无病生存期（DFS）采用Kaplan-Meier法估计，并使用多变量Cox比例风险模型。
结果
该队列包括非复发（43.9%）、复发（26.3%）、新辅助治疗进展（11.5%）和新发IV期（18.3%）病例。IM亚型（16.3%）在非复发病例中富集，其中位sTILs水平最高（20.0%）。BLIS（26.3%）和UC（39.4%）亚型在复发和转移性疾病中占主导地位，而MES亚型（9.0%）在新辅助化疗进展者中占主导地位。在早期疾病中，sTILs ≥10%独立预测更优的OS（HR 0.63，95% CI，0.40-1.0；P = .049），在新发IV期组中未显示预后作用。分子亚型在多变量模型中失去独立显著性。
展开英文摘要原文
BACKGROUND
Triple-negative breast cancer (TNBC) is a biologically heterogeneous, aggressive disease where immunohistochemistry (IHC)-based algorithms, defining luminal androgen receptor (LAR), immunomodulatory (IM), basal-like immunosuppressed (BLIS), mesenchymal (MES), and unclassifiable (UC) subtypes, offer a pragmatic alternative to transcriptomics. This study evaluated clinical trajectories and survival outcomes associated with IHC-based molecular subtypes and stromal tumor-infiltrating lymphocytes (sTILs) across distinct subgroups.
METHODS
A retrospective analysis of 289 women with TNBC treated with chemotherapy-only regimens analyzed molecular subtypes across four clinical groups: non-recurrent, recurrent, progression during neoadjuvant chemotherapy, and de novo metastatic disease. IHC-based subclassification included androgen receptor (AR), CD8, FOXC1, and DCLK1 biomarkers. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method, and multivariable Cox proportional hazards models.
RESULTS
The cohort included non-recurrent (43.9%), recurrent (26.3%), neoadjuvant progressors (11.5%), and de novo stage IV (18.3%) cases. IM subtype (16.3%) was enriched in non-recurrent cases with the highest median sTILs levels (20.0%). BLIS (26.3%) and UC (39.4%) subtypes predominated in recurrent and metastatic disease, while MES subtype (9.0%) predominated in neoadjuvant chemotherapy progressors. In early-stage disease, sTILs ≥10% independently predicted superior OS (HR 0.63, 95% CI, 0.40-1.0; P = .049), showing no prognostic role in the de novo stage IV group. Molecular subtypes lost independent significance in multivariable models.
CONCLUSIONS
Clinicopathological factors and sTILs remain primary prognostic determinants in TNBC. Although IHC-based molecular subtypes were not independent survival predictors, their differential clinical distribution validates their biological relevance to identify therapeutic vulnerabilities, and to guide precision medicine and de-escalation strategies.
论文信息
- 作者
- Hernandez-Hernandez JE、Mohar A、Lara-Torres CO、Vazquez-Juarez D、Palacios T、Peña-Torres L、Moncada-Claudio G、Velazquez-Martinez A
- 单位
- Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, Nuevo Leon, 64710, Mexico.Mexico
- 期刊
- The oncologist2026 Aug 6
- 原文标识
- PubMed 42587422 · DOI 10.1093/oncolo/oyag322
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