ATAD2 is a potential immunotherapy target for patients with small cell lung cancer harboring HLA-A∗0201

作者：Yuan Li, Sini Li, Yixiang Zhu, Lin Yang, Xue Zhang, Yan Qu, Zhijie Wang, Jianchun Duan, Jia Zhong, Yanhua Tian, Lihui Liu, Boyang Sun, Kailun Fei, Zheng Liu, Jian Zhang, Yan He, Yufeng Guo, Danming He, Wei Zhuang, Jinsong Zhang, Zixiao Ma, Hua Bai, Jie Wang · 发表于：EBioMedicine · 年份：2025 · DOI：10.1016/j.ebiom.2024.105515 · 被引用次数：4 · 研究领域：Lung Cancer Research Studies、Protein Degradation and Inhibitors、Cancer Immunotherapy and Biomarkers

BACKGROUND: Small cell lung cancer (SCLC) represents a highly aggressive neuroendocrine tumour with a dismal prognosis. Currently, the identification of a specific tumour antigen that can facilitate immune-based therapies for SCLC remains elusive. METHODS: We employed liquid chromatography-tandem mass spectrometry (LC-MS/MS) to analyse cancer/testis antigens (CTAs) in SCLC cell lines and human tumour specimens. Immunohistochemistry of clinical specimens was performed to compare protein expression in SCLC, non-small cell lung cancer (NSCLC), and matched normal-adjacent tissues. Additionally, publicly available RNA sequencing databases were interrogated to identify gene expression patterns in different SCLC subtypes and in different disease stages. FINDINGS: Distinct numbers and types of CTAs were identified across SCLC subtypes, with significantly higher expression levels of ATPase family AAA domain-containing protein 2 (ATAD2) observed in SCLC compared to normal adjacent tissues and NSCLC tissues. A dynamic expression pattern of ATAD2 was found throughout the clinical course of SCLC and exhibited a positive correlation with achaete-scute family bHLH transcription factor 1 (ASCL1) expression in SCLC. Immunopeptidomics analysis identified the YSDDDVPSV sequence derived from the HLA-A∗02:01 restriction epitope of ATAD2 as a highly promising tumour antigen candidate for potential immunotherapy applications. YSDDDVPSV immunopeptides were confirmed to be present in SCLC-A and SCLC-...