LTF as a Potential Predictive Biomarker for Durable Benefit From First‐Line Chemo‐Immunotherapy in Small Cell Lung Cancer

作者：Shimo Shen, Yili Wu, Zhuowei Shao, You Li, Di Peng, Bing Li, Zhou Zhang, Shibo Wu · 发表于：Cancer Science · 年份：2025 · DOI：10.1111/cas.70049 · 被引用次数：3 · 研究领域：Lung Cancer Research Studies、Neuroendocrine Tumor Research Advances、Chromatin Remodeling and Cancer

At present, only a limited fraction of patients with extensive-stage small cell lung cancer (ES-SCLC) achieve a sustained response to immune checkpoint blockade (ICB) therapy. The factors that drive therapeutic efficacy remain poorly delineated, and the field is devoid of reliable predictive biomarkers to guide personalized treatment decisions. Therefore, we conducted RNA sequencing of tumor samples from 21 patients prior to treatment to identify expression patterns associated with lasting benefit and used weighted gene co-expression network analysis (WGCNA) to identify key genes associated with favorable outcomes of chemotherapeutic immunotherapy. Multiplex immunofluorescence (mIF) quantification and reanalysis of publicly available datasets were used to validate the hub gene's association with the immune microenvironment and immunotherapy efficacy. The functional significance of the hub gene was further investigated in cellular models. We found that the durable clinical benefit (DCB) group exhibited significantly elevated levels of inflammation and interferon response compared to the no-durable benefit (NDB) group, alongside a notably lower proportion of Tregs and distinct metabolic features. Lactotransferrin (LTF) was identified as a hub gene associated with durable therapeutic benefits in chemo-immunotherapy. By further analysis, we proved that LTF acts as a tumor suppressor in small cell lung cancer, impacting cell proliferation, migration, and invasiveness. It also inhi...