Liquid biopsy using plasma proteomics in predicting efficacy and tolerance of PD-1/PD-L1 blockades in NSCLC: a prospective exploratory study

作者：Yuan Gao, Qi Fei, Wenhao Zhou, Peng Jiang, Mingming Hu, Ying Wang, Congcong Song, Yi Han, Dongdong Li, Na Qin, Hongmei Zhang, Haitao Luo, Tongmei Zhang, Hongxia Li · 发表于：Molecular Biomedicine · 年份：2025 · DOI：10.1186/s43556-025-00291-6 · 被引用次数：13 · 研究领域：Cancer Immunotherapy and Biomarkers、Ferroptosis and cancer prognosis、Lung Cancer Treatments and Mutations

Immune checkpoint inhibitors (ICIs) show limited efficacy in non-small cell lung cancer (NSCLC), highlighting the need for predictive biomarkers. Here we prospectively analysed serial plasma samples from 34 ICI-treated advanced NSCLC patients (plus 30 validation samples) using the Olink Immuno-Oncology panel. We assessed dynamic proteomic changes associated with ICI efficacy and immune-related adverse events (irAEs), and developed a prognostic model. Following ICIs, 42/92 proteins significantly elevated upon ICI treatment (p < 0.05). Baseline levels of CD28, CXCL10, and TNFSF14, and increased CD40L post-treatment, correlated with inferior response. Baseline IL-4, IL-13 and increased GZMA post-treatment were associated with irAE occurrence. Using LASSO-Cox regression, we established an Immunosuppressive Signature of Combined Resistance Elements (I-SCORE) model based on eight plasma proteins (CCL23, ARG1, CD83, ADA, CXCL10, TNFSF14, CD28, GZMA). I-SCORE demonstrated strong predictive power for overall survival (12-month AUC = 0.94), progression-free survival (12-month AUC = 0.75), and treatment response (AUC = 0.62). Furthermore, a high I-SCORE was demonstrated to reflect an inflammatory and immunosuppressive phenotype, showing positive linear relationships with plasma IL-6, IL-8, IL-10, and monocyte count, and negative relationships with IL-33 and active T-cell proportion. Our study identifies I-SCORE, derived from plasma proteomics, as a promising integrated biomarker for pre...