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:TCL1A+ B cells predict prognosis in triple-negative breast cancer through integrative analysis of single-cell and bulk transcriptomic data.
TCL1A+ B cells predict prognosis in triple-negative breast cancer through integrative analysis of single-cell and bulk transcriptomic data.
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三阴性乳腺癌(TNBC)是一种侵袭性亚型,治疗选择有限且死亡率较高。目前临床上仍亟需判断患者是否能从化疗等治疗中获益。通过整合单细胞和整体转录组数据,我们首次鉴定出与TNBC预后相关的TCL1A⁺ B细胞功能。这拓展了传统TIL(肿瘤浸润淋巴细胞)用于预测生存的研究视角,尤其凸显B细胞在TNBC中的潜在价值。研究收集5例TNBC患者的单细胞RNA测序数据,分析免疫细胞群与临床结局的关联;功能分析基于MsigDB通路开展基因集富集分析。随后依据TCL1A⁺ B细胞与其他免疫细胞差异表达基因构建其基因特征,用于探索其与肿瘤微环境(TME)的关联,并采用非参数无监督方法建立预后特征。研究鉴定出TCL1A⁺ B细胞这一与TNBC临床结局相关的B细胞簇。功能分析显示其参与B细胞活化和免疫应答调节。TCL1A⁺ B细胞群高度富集与具有抗肿瘤作用的炎性TME相关。TCL1A⁺ B细胞丰度较高与较好的治疗结局正相关,表现为总生存期延长。
本研究提示,TCL1A⁺ B细胞在TNBC治疗和预后预测中发挥关键作用,但仍需进一步研究验证。整合不同分辨率的转录组数据,也为发现新型预后标志物提供了可行方法。
Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options and high mortality rates. It remains a prevailing clinical need to distinguish whether the patient can benefit from therapy, such as chemotherapy. By integrating single-cell and global transcriptome data, we have for the first time identified TCL1A+ B cell functions that are prognostically relevant in TNBC. This finding broadens the perspective of traditional tumor-infiltrating lymphocytes in predicting survival, especially the potential value of B cells in TNBC.
Single-cell RNA-seq data from five TNBC patients were collected to identify the association between immune cell populations and clinical outcomes. Functional analysis was according to gene set enrichment analysis using pathways from MsigDB. Subsequently, the gene signature of TCL1A+ B cells based on differential expression genes of TCL1A+ B cells versus other immune cells was used to explore the correlation with tumor microenvironment (TME) and construct a prognostic signature using a non-parametric and unsupervised method.
We identified TCL1A+ B cells as a cluster of B cells associated with clinical outcomes in TNBC. Functional analysis demonstrated its function in B cell activation and regulation of immune response. The highly enriched TCL1A+ B cell population was found to be associated with a thermal TME with anti-tumor effects.
A high abundance of TCL1A+ B cell population is positively correlated with a favorable therapeutic outcome, as indicated by longer overall survival. The present study suggests that TCL1A+ B cells play a key role in the treatment and prognostic prediction of TNBC, although further studies are needed to validate our findings.
Moreover, the integration of transcriptome data at various resolutions provides a viable approach for the discovery of novel prognostic markers.
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