外周血单核细胞（PBMC）反映癌症进展过程中的全身免疫反应。然而，对癌症患者 PBMC 的组成和功能缺乏全面的了解，这些特征辅助癌症诊断的潜力也不清楚。在这里，通过单细胞 RNA 测序 (scRNA-seq) 研究了癌症患者和健康捐赠者 PBMC 的成分和状态差异，涉及来自 68 个癌症样本和 14 个健康样本的 262 025 个 PBMC。我们观察到癌症患者中大多数免疫亚群的激活和分化增强，同时幼稚 T 细胞减少、巨噬细胞扩增、NK 细胞和骨髓细胞受损，以及肿瘤促进和免疫抑制。基于从每种主要细胞类型的权重基因共表达网络分析（WGCNA）模块中识别出的差异细胞类型丰度和/或中心基因等特征，我们应用逻辑回归来构建癌症诊断模型。此外，我们发现上述模型可以高灵敏度地区分癌症患者和健康供体。我们的研究为在非侵入性癌症诊断中使用 PBMC 的功能提供了新的见解。© 作者 2023。由牛津大学出版社出版。版权所有。如需权限，请发送电子邮件至：journals.permissions@oup.com。

Peripheral blood mononuclear cells (PBMCs) reflect systemic immune response during cancer progression. However, a comprehensive understanding of the composition and function of PBMCs in cancer patients is lacking, and the potential of these features to assist cancer diagnosis is also unclear. Here, the compositional and status differences between cancer patients and healthy donors in PBMCs were investigated by single-cell RNA sequencing (scRNA-seq), involving 262 025 PBMCs from 68 cancer samples and 14 healthy samples. We observed an enhanced activation and differentiation of most immune subsets in cancer patients, along with reduction of naïve T cells, expansion of macrophages, impairment of NK cells and myeloid cells, as well as tumor promotion and immunosuppression. Based on characteristics including differential cell type abundances and/or hub genes identified from weight gene co-expression network analysis (WGCNA) modules of each major cell type, we applied logistic regression to construct cancer diagnosis models. Furthermore, we found that the above models can distinguish cancer patients and healthy donors with high sensitivity. Our study provided new insights into using the features of PBMCs in non-invasive cancer diagnosis.© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.