Tumor cell-intrinsic BIN1 deficiency promotes the immunosuppression and impedes ferroptosis of non-small cell lung cancer via G3BP1-mediated degradation of STAT1

作者：Jiali Wang, Yunlong Jia, Tianxu Liu, Xinyan Liu, Shuxian Yin, Jiaqi Chen, Xiaoqing Xu, Yi Zhang, Lihua Liu · 发表于：Journal of Experimental & Clinical Cancer Research · 年份：2025 · DOI：10.1186/s13046-025-03404-9 · 被引用次数：9 · 研究领域：Ferroptosis and cancer prognosis、Cancer Immunotherapy and Biomarkers、Immune cells in cancer

Abstract Background Tumors often evade immune surveillance by limiting T cell infiltration. In non-small cell lung cancer (NSCLC), increased infiltration of CD8 + T cells is associated with a favorable response to immunotherapy. While BIN1 is recognized as a tumor suppressor gene, its role in shaping the tumor microenvironment in NSCLC has yet to be fully clarified. Methods To investigate the relationship between BIN1 expression and CD8 + T cell infiltration in NSCLC, we performed a comprehensive data analysis utilizing clinical information from NSCLC patients. BIN1 expression levels in NSCLC tissues were evaluated, and their correlation with CD8 + T cells infiltration and patient survival outcomes was examined. Loss-of-function strategies targeting BIN1 were applied in syngeneic NSCLC mouse models to assess its functional significance. Tumor growth was monitored, and immune cell populations were analyzed in terms of frequency and functionality through mass cytometry and flow cytometry techniques. Cytokine secretion was profiled using multiplex assays. Additionally, RNA sequencing, immunoprecipitation-mass spectrometry, and molecular docking were employed to confirm direct interactions between BIN1 and cytokine-encoding genes. Finally, the regulatory role of BIN1 in ferroptosis in NSCLC cells were explored using metabolomics analysis, ROS measurement, and MDA detection. Results We observed that BIN1 expression is downregulated in NSCLC tumor tissues, with its reduced expressi...