A pan-cancer analysis revealed SKP2 as an inhibitor of the tumor immune microenvironment and a promising therapeutic target for immunotherapy

作者：Xingyu Liao, Yaxin Zhang, Xue Yu, Wei Du, Linxi Chen, Zhiqing Zhao, Haijie Liang, Xingyu Liu, Feiyang Qi, David S. Geller, Rui Yang, Bang H. Hoang, Li Hu, Jichuan Wang · 发表于：Precision Clinical Medicine · 年份：2025 · DOI：10.1093/pcmedi/pbaf022 · 被引用次数：2 · 研究领域：Cancer Immunotherapy and Biomarkers、Lymphoma Diagnosis and Treatment、RNA modifications and cancer

Abstract Background S-Phase kinase associated protein 2 (SKP2) is a key regulator of the cell cycle and proliferation linked to cancer development. Our recent study has revealed that knocking out Skp2 in a mouse model significantly activates anti-tumor immunity. Although several studies have examined SKP2 in relation to the tumor immune microenvironment using public datasets, a comprehensive pan-cancer evaluation that integrates multi-omics layers and in vivo validation has remained limited. Methods In this study, we integrated multi-omics data from diverse public datasets to comprehensively analyze SKP2 expression characteristics and its relationship to tumor immunity across pan-cancer. A multiplex immunofluorescence assay was performed on tumors from Skp2 knockout and Skp2-intact mouse models for validation. Results Our findings indicate that SKP2 is overexpressed in various cancer types, leading to poor prognosis. Single-cell transcriptomic analyses further revealed that SKP2 is predominantly expressed in malignant and immune cells. Notably, a multiplex immunofluorescence assay on tumors from Skp2 knockout and Skp2-intact mouse models and pan-cancer data unveiled a correlation between SKP2 and the “immune-cold” microenvironment, which, possibly linked to the weakened antigen presentation, reduced secretion of chemokines in SKP2-overexpressing cancers. Additionally, we observed that SKP2 overexpression predicts worse immunotherapy efficacy. Conclusion Our findings provide n...