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TIL(肿瘤浸润淋巴细胞)呈现与 TNBC 患者化疗反应相关的预后特征

英文原题:Tumor-infiltrating lymphocytes display prognostic signatures associated with chemotherapy response in TNBC patients.

查看英文原题

Tumor-infiltrating lymphocytes display prognostic signatures associated with chemotherapy response in TNBC patients.

PubMed 2026/06/08(内容时间) iScience Q1 · IF 4.5(JCR 2025)

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中文摘要

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。

展开英文摘要原文

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.

论文信息

作者
Banerjee S、Tiwari VK、Raman K、Inayatullah M
第一作者单位
Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology (IIT) Madras, Chennai 600 036, India.India
通讯作者单位
Institute for Molecular Medicine, University of Southern Denmark, Odense M, Denmark.Denmark
期刊
iScience2026 Jun 19
原文标识
PubMed 42291245 · DOI 10.1016/j.isci.2026.116295