Abstract 6788: Spatial single-cell analysis reveals stage-dependent mechanisms of anti-IL-1β therapy in lung adenocarcinoma

作者：Bo Zhu, Muhammad Aminu, Yanhua Tian, Shao-Wei Lu, Ou Shi, Wei Lu, Hong Chen, Hui Li, Zhubo Wei, Monique B. Nilsson, LM Solis Soto, Futreal P. Andrew, Don L. Gibbons, John Victor Heymach, Chao Cheng, Jia Wu, J. Zhang · 发表于：Cancer Research · 年份：2026 · DOI：10.1158/1538-7445.am2026-6788 · 被引用次数：1 · 研究领域：Single-cell and spatial transcriptomics、Extracellular vesicles in disease、interferon and immune responses

Abstract Introduction: Lung adenocarcinoma (LUAD) is a leading cause of cancer mortality, with IL-1β-driven inflammation playing a central role in tumor progression. Although IL-1β blockade shows promising antitumor effects, its efficacy varies across tumor stages, and the mechanisms behind this stage-dependent response remain unclear. Here, we investigate how tumor-immune interactions and microenvironmental remodeling shape differential responses to anti-IL-1β therapy during LUAD progression. Methods: We performed spatial single-cell analysis of the immune microenvironment using Visium HD on human (10 adjacent normal, 17 AAH, 12 IAC) and mouse samples (21 adjacent normal, 57 hyperplasia, 13 IAC). Integrating these data with stage-matched scRNA-seq, we mapped IL-1β-IL1R1-mediated cell-cell interactions across LUAD stages. Long-term anti-IL-1β treatment was evaluated in two mouse models—C57BL/6 Kras^G12D (early: 4-14 weeks; late: 20-30 weeks) and 129S4 urethane-induced (early: 4-14 weeks; late: 30-40 weeks)—with efficacy and mechanisms assessed via scRNA-seq and Xenium 5K. Short-term treatments (0, 6, 30 weeks) in C57BL/6 Kras^G12D were performed to further explore mechanisms. Results: In human tissues, IL-1β-IL1R1 interactions (“IL-1βnets”) occurred primarily between myeloid cells and fibroblasts, epithelial, and endothelial cells, a pattern conserved in mouse tissues. Long-term anti-IL-1β treatment was effective only at the early stage. Early-stage scRNA-seq showed enhanced ...