RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
一份全面的单细胞乳腺肿瘤图谱界定上皮与免疫异质性及预测抗 PD-1 治疗反应的相互作用
英文原题：A comprehensive single-cell breast tumor atlas defines epithelial and immune heterogeneity and interactions predicting anti-PD-1 therapy response.
查看英文原题
A comprehensive single-cell breast tumor atlas defines epithelial and immune heterogeneity and interactions predicting anti-PD-1 therapy response.
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中文摘要
我们构建了原发性乳腺肿瘤微环境（TME）的整合单细胞RNA测序图谱，纳入8个数据集中的119份活检样本，共236,363个细胞。本研究利用该资源开展多项免疫细胞和癌上皮细胞异质性分析。我们将乳腺TME中的自然杀伤（NK）细胞划分为6个亚群，以描述其异质性。由于NK细胞异质性与上皮细胞异质性相关，我们从单基因表达、分子亚型和反映肿瘤内转录异质性的10类特征等层面表征上皮细胞。我们开发了InteractPrint，用于评估癌上皮细胞异质性如何影响癌症-免疫相互作用。我们进一步利用T细胞InteractPrint预测两项新辅助抗PD-1乳腺癌临床试验中的免疫检查点抑制（ICI）应答。两项试验中，T细胞InteractPrint均可预测应答，优于PD-L1（AUC分别为0.82和0.83，而PD-L1分别为0.50和0.72）。该资源可支持对乳腺TME开展更多高分辨率研究。
展开英文摘要原文
We present an integrated single-cell RNA sequencing atlas of the primary breast tumor microenvironment (TME) containing 236,363 cells from 119 biopsy samples across eight datasets. In this study, we leverage this resource for multiple analyses of immune and cancer epithelial cell heterogeneity.
We define natural killer (NK) cell heterogeneity through six subsets in the breast TME. Because NK cell heterogeneity correlates with epithelial cell heterogeneity, we characterize epithelial cells at the level of single-gene expression, molecular subtype, and 10 categories reflecting intratumoral transcriptional heterogeneity.
We develop InteractPrint, which considers how cancer epithelial cell heterogeneity influences cancer-immune interactions.
We use T cell InteractPrint to predict response to immune checkpoint inhibition (ICI) in two breast cancer clinical trials testing neoadjuvant anti-PD-1 therapy. T cell InteractPrint was predictive of response in both trials versus PD-L1 (AUC = 0. 82, 0. 83 vs. 0. 50, 0. 72). This resource enables additional high-resolution investigations of the breast TME.
论文信息
- 作者
- Xu L、Saunders K、Huang SP、Knutsdottir H、Martinez-Algarin K、Terrazas I、Chen K、McArthur HM
- 第一作者单位
- Department of Internal Medicine, Division of Hematology and Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.United States
- 通讯作者单位
- Department of Internal Medicine, Division of Hematology and Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA; Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address: isaac.chan@utsouthwestern.edu.United States
- 期刊
- Cell reports. Medicine2024 May 21
- 原文标识
- PubMed 38614094 · DOI 10.1016/j.xcrm.2024.101511
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