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
英文原题:Tumor-infiltrating lymphocytes display prognostic signatures associated with chemotherapy response in TNBC patients.
Tumor-infiltrating lymphocytes display prognostic signatures associated with chemotherapy response in TNBC patients.
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三阴性乳腺癌(TNBC)是一种侵袭性亚型,常对新辅助化疗(NAC)耐药;TIL(肿瘤浸润淋巴细胞)是应答的重要预测因素。研究者利用治疗前TNBC肿瘤的单细胞RNA测序数据集,识别出一种由80个基因构成的TIL特异性特征,可反映免疫活化并依据TIL丰度对肿瘤分层。通路分析显示免疫调节程序富集,包括与适应性免疫活性一致的移植物排斥通路。在单细胞及整体数据集中的验证显示,该特征与良好治疗应答和无复发生存相关。通过多阶段特征筛选流程将面板精简至30个基因,在11个独立TNBC队列(n=680)中预测病理完全缓解与残余病变的表现良好,ROC曲线下面积(AUROC)均值为0.77。网络分析识别出共识枢纽基因,包括T细胞信号传导中的CD8A、LCK和CTLA4。调控分析发现一组保守的TIL相关转录因子,支持该免疫特征在TNBC分层及治疗靶向策略中的临床应用价值。
Triple-negative breast cancer (TNBC) is an aggressive subtype often resistant to neoadjuvant chemotherapy (NAC), and tumor-infiltrating lymphocytes (TILs) are important predictors of response. Using single-cell RNA sequencing datasets of pre-treated TNBC tumors, we identified an 80-gene TIL-specific signature that captures immune activation and stratifies tumors by TIL abundance. Pathway analysis showed enrichment of immune-regulatory programs, including allograft rejection, consistent with adaptive immune activity. Validation across single-cell and bulk datasets linked the signature to favorable response and relapse-free survival.
A multi-stage feature selection pipeline refined the panel to 30 genes, achieving strong prediction of pathological complete response versus residual disease across eleven independent TNBC cohorts ( n = 680; mean area under the ROC curve [AUROC] = 0. 77).
Network analysis identified consensus hub genes, including CD8A , LCK , and CTLA4 , central to T cell signaling. Regulatory analysis revealed a conserved set of TIL-associated transcription factors, supporting an immune program with clinical utility in TNBC stratification and therapeutic targeting strategies.
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