Integrated cellular, proteomic and metabolomic profiling of immune-related adverse events in non-small cell lung cancer

作者：Smith NJ, Gunasegaran B, McLean A, Kohonen-Corish MRJ, Bucca A, Checkley J, Lee JH, Liu JJ, Kao S, Boyer M, Mander K, Brown B, Wang XS, O'Sullivan JF, Fazekas de St Groth B, McGuire HM · 发表于：Frontiers in immunology · 年份：2026 · DOI：10.3389/fimmu.2026.1911262 · 被引用次数：116 · 研究领域：Carcinoma, Non-Small-Cell Lung、Lung Neoplasms、Proteomics、Metabolomics、Immune Checkpoint Inhibitors、Metabolome、Humans、Male、Female、Aged、Middle Aged、Immunophenotyping

INTRODUCTION: Immune checkpoint inhibitor (ICI) therapy has become standard of care for late stage non-small cell lung cancer (NSCLC), producing durable responses in a subset of patients. However, inflammatory side eKects termed immune-related adverse events (irAEs) occur in up to 40% of ICI-treated NSCLC patients. Current approaches to alleviate irAEs include treatment with immune-suppressing corticosteroids. However, these treatments may undermine the eKicacy of ICIs by suppressing both the irAE and the anti-tumour immune response. To identify more specific therapeutic targets, a better understanding of the complex immunopathology underlying the development of irAEs in NSCLC is required. METHODS: In this study, pre-treatment blood samples were prospectively collected from 72 NSCLC patients, including 23 who subsequently developed irAEs. Of these 72 samples, PBMCs from 59 were characterised using high-parameter mass cytometry. Plasma from 30 samples was analysed using the SomaScan platform that provides in depth characterisation of over 10,000 proteins, and the plasma metabolome of 30 samples was explored using liquid chromatograph-mass spectrometry (LC-MS). RESULTS: A unique peripheral immunophenotype was observed in patients who subsequently developed irAEs, characterised by decreased memory B cell abundance, heightened Th2 immunity, and an increase in plasma cytokines. Investigation into baseline metabolites revealed dysregulation of fatty acid metabolism associated wit...