Molecular and immunological features associated with long-term benefits in metastatic NSCLC patients undergoing immune checkpoint blockade

作者：Pedro Rocha, Rafael Bach, Laura Masfarré, Sharia Hernandez, N. Navarro-Gorro, A. Rossell, Xavier Villanueva, Mario Giner, Ignacio Sánchez, Miguel Galindo‐Campos, R. Del Rey-Vergara, Albert Iñañez, Beatriz Sánchez‐Espiridión, Wei Lü, Ariadna Acedo-Terrades, Pau Berenguer‐Molins, Albert Sánchez‐Font, Roberto Chalela, Víctor Curull, Álvaro Taus, Max Hardy-Werbin, Mark Sausen, Andrew Georgiadis, James R. White, Jennifer Jackson, Laura Moliner, Sergi Clavé, Beatríz Bellosillo, Ana Rovira, Ignacio I. Wistuba, Luisa M. Solis Soto, Júlia Perera‐Bel, Edurne Arriola · 发表于：OncoImmunology · 年份：2025 · DOI：10.1080/2162402x.2025.2469377 · 被引用次数：8 · 研究领域：Cancer Immunotherapy and Biomarkers、Lung Cancer Research Studies、Ferroptosis and cancer prognosis

Introduction Immunotherapy is firmly established as a treatment regimen in various solid tumors, driven by its exceptional benefits in a selected group of patients. Despite widespread adoption of immune checkpoint blockade (ICB) across diverse solid tumors, the quest for a clinically informative biomarker for long-term benefit remains unmet.Methods A total of 49 patients with metastatic NSCLC treated with ICB were included. Long-term (LTR) and short-term responders (STR) were defined as those with a response to ICB lasting more than 24 months or less than 6 months, respectively. Longitudinal blood specimens were collected before ICB treatment initiation and early-on treatment. Plasma ctDNA next-generation sequencing panel (NGS) and serum proteomics were performed. GeoMx DSP on baseline tumor tissue was performed in a subset of patients.Results Our analysis revealed specific characteristics of LTR compared with STR, namely higher PD-L1 in tumor cells (p = 0.005) and higher incidence of irAEs (p = 0.001). Genomic features associated with lack of benefit from ICB included co-occurring mutations in KRAS/STK11 and TP53/KMT2D (p < 0.05). At a baseline, LTR patients exhibited higher serum levels of proteins related with apoptosis (CASP8, PRKRA), chemotaxis, immune proteasome, processing of MHC class I (S100A4, PSMD9, RNF41) and immune homeostasis (HAVCR1, ARG1) (p < 0.05). Protein spatial profiling of tumor samples showed higher levels of proteins linked with the presence of immune ...