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
英文原题:SPARTIN: a Bayesian method for the quantification and characterization of cell type interactions in spatial pathology data.
SPARTIN: a Bayesian method for the quantification and characterization of cell type interactions in spatial pathology data.
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在本文中,我们提出了SPatial Analysis of paRtitioned Tumor-Immune imagiNg(SPARTIN),一种从病理图像中对免疫细胞浸润进行空间量化的贝叶斯方法。SPARTIN使用贝叶斯点过程来表征一种新的局部肿瘤-免疫细胞相互作用度量,即细胞类型相互作用概率(CTIP)。CTIP允许严格纳入不确定性,并且具有高度可解释性,无论是在活检内部还是跨活检之间,均可用于评估与基因组和临床特征的关联。
通过模拟,我们表明SPARTIN与现有方法相比能够准确区分各种细胞相互作用模式。使用SPARTIN,我们表征了335例黑色素瘤活检内部及之间的局部空间免疫细胞浸润,并评估了其与基因组、表型和临床结局的关联。我们发现CTIP与去卷积免疫细胞患病率评分(包括CD8+ T-Cells和Natural Killer cells)显著(负向)相关。此外,平均CTIP评分在先前建立的转录组类别之间差异显著,并与生存结局显著相关。讨论:SPARTIN 为在高分辨率数字组织病理学成像数据中研究空间细胞相互作用及其与患者层面特征的关联提供了一个通用框架。我们的分析结果在皮肤黑色素瘤背景下对治疗和预后均具有潜在意义。SPARTIN 的 R 包可在 https://github.com/bayesrx/SPARTIN 获取,图像和结果的可视化工具可在 https://nateosher.github.io/SPARTIN 获取。
Introduction: The acquisition of high-resolution digital pathology imaging data has sparked the development of methods to extract context-specific features from such complex data. In the context of cancer, this has led to increased exploration of the tumor microenvironment with respect to the presence and spatial composition of immune cells. Spatial statistical modeling of the immune microenvironment may yield insights into the role played by the immune system in the natural development of cancer as well as downstream therapeutic interventions. Methods: In this paper, we present SPatial Analysis of paRtitioned Tumor-Immune imagiNg (SPARTIN), a Bayesian method for the spatial quantification of immune cell infiltration from pathology images.
SPARTIN uses Bayesian point processes to characterize a novel measure of local tumor-immune cell interaction, Cell Type Interaction Probability (CTIP). CTIP allows rigorous incorporation of uncertainty and is highly interpretable, both within and across biopsies, and can be used to assess associations with genomic and clinical features.
Results: Through simulations, we show SPARTIN can accurately distinguish various patterns of cellular interactions as compared to existing methods. Using SPARTIN, we characterized the local spatial immune cell infiltration within and across 335 melanoma biopsies and evaluated their association with genomic, phenotypic, and clinical outcomes.
We found that CTIP was significantly (negatively) associated with deconvolved immune cell prevalence scores including CD8+ T-Cells and Natural Killer cells.
Furthermore, average CTIP scores differed significantly across previously established transcriptomic classes and significantly associated with survival outcomes. Discussion: SPARTIN provides a general framework for investigating spatial cellular interactions in high-resolution digital histopathology imaging data and its associations with patient level characteristics.
The results of our analysis have potential implications relevant to both treatment and prognosis in the context of Skin Cutaneous Melanoma. The R-package for SPARTIN is available at https://github. com/bayesrx/SPARTIN along with a visualization tool for the images and results at: https://nateosher. github. io/SPARTIN.
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