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Comprehensive peripheral blood immunoprofiling reveals five immunotypes with immunotherapy response characteristics in patients with cancer
Cancer Cell ( IF 50.3 ) Pub Date : 2024-05-13 , DOI: 10.1016/j.ccell.2024.04.008
Daniiar Dyikanov , Aleksandr Zaitsev , Tatiana Vasileva , Iris Wang , Arseniy A. Sokolov , Evgenii S. Bolshakov , Alena Frank , Polina Turova , Olga Golubeva , Anna Gantseva , Anna Kamysheva , Polina Shpudeiko , Ilya Krauz , Mary Abdou , Madison Chasse , Tori Conroy , Nicholas R. Merriam , Julia E. Alesse , Noel English , Boris Shpak , Anna Shchetsova , Evgenii Tikhonov , Ivan Filatov , Anastasia Radko , Anastasiia Bolshakova , Anastasia Kachalova , Nika Lugovykh , Andrey Bulahov , Anastasiia Kilina , Syimyk Asanbekov , Irina Zheleznyak , Pavel Skoptsov , Evgenia Alekseeva , Jennifer M. Johnson , Joseph M. Curry , Alban J. Linnenbach , Andrew P. South , EnJun Yang , Kirill Morozov , Anastasiya Terenteva , Lira Nigmatullina , Dmitry Fastovetz , Anatoly Bobe , Linda Balabanian , Krystle Nomie , Sheila T. Yong , Christopher J.H. Davitt , Alexander Ryabykh , Olga Kudryashova , Cagdas Tazearslan , Alexander Bagaev , Nathan Fowler , Adam J. Luginbuhl , Ravshan I. Ataullakhanov , Michael F. Goldberg

The lack of comprehensive diagnostics and consensus analytical models for evaluating the status of a patient’s immune system has hindered a wider adoption of immunoprofiling for treatment monitoring and response prediction in cancer patients. To address this unmet need, we developed an immunoprofiling platform that uses multiparameter flow cytometry to characterize immune cell heterogeneity in the peripheral blood of healthy donors and patients with advanced cancers. Using unsupervised clustering, we identified five immunotypes with unique distributions of different cell types and gene expression profiles. An independent analysis of 17,800 open-source transcriptomes with the same approach corroborated these findings. Continuous immunotype-based signature scores were developed to correlate systemic immunity with patient responses to different cancer treatments, including immunotherapy, prognostically and predictively. Our approach and findings illustrate the potential utility of a simple blood test as a flexible tool for stratifying cancer patients into therapy response groups based on systemic immunoprofiling.

中文翻译:

全面的外周血免疫分析揭示了癌症患者具有免疫治疗反应特征的五种免疫类型

由于缺乏评估患者免疫系统状态的综合诊断和共识分析模型,阻碍了免疫分析技术在癌症患者治疗监测和反应预测中的广泛应用。为了解决这一未满足的需求,我们开发了一个免疫分析平台,该平台使用多参数流式细胞术来表征健康捐献者和晚期癌症患者外周血中免疫细胞的异质性。使用无监督聚类,我们确定了五种免疫类型,它们具有不同细胞类型和基因表达谱的独特分布。使用相同方法对 17,800 个开源转录组进行的独立分析证实了这些发现。开发了基于连续免疫类型的特征评分,以将系统免疫与患者对不同癌症治疗(包括免疫治疗)的反应、预后和预测相关联。我们的方法和研究结果表明,简单的血液测试作为一种灵活的工具,可以根据系统免疫分析将癌症患者分为治疗反应组。
更新日期:2024-05-13
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