综合多组学揭示腺苷信号传导可预测免疫治疗反应并调节黑色素瘤的肿瘤生态系统。
Integrated multiomics revealed adenosine signaling predict immunotherapy response and regulate tumor ecosystem of melanoma.
发表日期:2024 Sep 15
作者:
Yantao Xu, Poyee Lau, Xiang Chen, Shuang Zhao, Yi He, Zixi Jiang, Xiang Chen, Guanxiong Zhang, Hong Liu
来源:
Human Genomics
摘要:
细胞外腺苷广泛参与调节肿瘤微环境。鉴于腺苷靶向治疗试验的结果令人失望,可能需要根据个体患者的微环境状态进行个性化治疗。在这里,我们介绍了使用公开的黑色素瘤数据集使用非负矩阵分数识别患者亚型的腺苷信号评分(ADO-score)模型,该模型旨在分析腺苷信号相关基因并构建预测预后的模型。我们分析了 580 个恶性黑色素瘤样本,并证明了其对预后的强大价值。对免疫检查点抑制剂数据集的进一步研究表明其作为免疫检查点抑制剂功效的分层因素的潜力。我们在湘雅医院黑色素瘤队列中验证了 ADO 评分在蛋白质水平免疫荧光方面的功效。更重要的是,单细胞和空间转录组数据强调了腺苷信号相关基因的细胞特异性表达模式以及黑色素瘤中肿瘤细胞和免疫细胞之间腺苷信号介导的串扰的存在。我们的研究揭示了腺苷信号传导与黑色素瘤患者的临床益处之间的紧密联系,并提出了一种在基因表达谱和组织学切片中普遍适用的腺苷信号传导模型,即 ADO 评分。该模型使我们能够更准确、更方便地选择可能从免疫治疗中受益的患者。© 2024。作者。
Extracellular adenosine is extensively involved in regulating the tumor microenvironment. Given the disappointing results of adenosine-targeted therapy trials, personalized treatment might be necessary, tailored to the microenvironment status of individual patients. Here, we introduce the adenosine signaling score (ADO-score) model using non-negative matrix fraction identified patient subtypes using publicly available melanoma dataset, which aimed to profile adenosine signaling-related genes and construct a model to predict prognosis. We analyzed 580 malignant melanoma samples and demonstrated its robust value for prognosis. Further investigation in immune checkpoint inhibitor dataset suggests its potential as a stratified factor of immune checkpoint inhibitor efficacy. We validated the power of the ADO-score at the protein level immunofluorescence in a melanoma cohort from Xiangya Hospital. More importantly, single-cell and spatial transcriptomic data highlighted the cell-specific expression patterns of adenosine signaling-related genes and the existence of adenosine signaling-mediated crosstalk between tumor cells and immune cells in melanoma. Our study reveals a robust connection between adenosine signaling and clinical benefits in melanoma patients and proposes a universally applicable adenosine signaling model, the ADO-score, in gene expression profiles and histological sections. This model enables us to more precisely and conveniently select patients who are likely to benefit from immunotherapy.© 2024. The Author(s).