文章：

JAVELIN Bladder 100研究中尿路上皮癌患者血液表观遗传生物标志物与肿瘤免疫表型的关联分析

Blood-Epigenetic Biomarker Associations with Tumor Immunophenotype in Patients with Urothelial Carcinoma from JAVELIN Bladder 100

原文发布日期：14 July 2025

DOI: 10.3390/cancers17142332

类型: Article

开放获取: 是

英文摘要：

Background/Objectives: Response to immune checkpoint inhibitors (ICIs) is associated with several biological pathways, including tumor immunogenicity and antitumor immunity. Identifying host factors involved in these pathways may guide personalized ICI treatment. Methods: We describe the application of chromatin conformation assays to blood from patients with advanced urothelial carcinoma from the phase 3 JAVELIN Bladder 100 trial (NCT02603432). This trial demonstrated a significant survival benefit with avelumab maintenance plus best supportive care (BSC) vs. BSC alone following non-progression with platinum-based chemotherapy as first-line therapy. Blood-based chromatin conformation markers (CCMs) were screened for associations with high/low immune effector gene expression in tumors and for interactions with outcomes and tumor mutation burden. Results: Candidate CCMs included genes involved in several immune response pathways, such asPOU2F2, which encodes a transcription factor that regulates B-cell maturation. Conclusions: Our findings suggest that polygenic host factors may affect response to ICIs and support further investigation of chromatin conformation assays.

摘要翻译： 

背景/目的：对免疫检查点抑制剂（ICIs）的应答与多种生物学通路相关，包括肿瘤免疫原性和抗肿瘤免疫。识别参与这些通路的宿主因素可能有助于指导个体化的ICI治疗。方法：我们描述了染色质构象检测在JAVELIN Bladder 100三期临床试验（NCT02603432）中晚期尿路上皮癌患者血液样本中的应用。该试验证实，对于一线含铂化疗后未进展的患者，与单纯最佳支持治疗（BSC）相比，avelumab维持治疗联合BSC可显著延长生存期。我们筛选了基于血液的染色质构象标志物（CCMs），分析其与肿瘤中高/低免疫效应基因表达的相关性，以及与临床结局和肿瘤突变负荷的交互作用。结果：候选CCMs涉及多个免疫应答通路相关基因，例如编码调控B细胞成熟转录因子的POU2F2基因。结论：我们的研究结果表明，多基因宿主因素可能影响对ICIs的应答，并支持进一步开展染色质构象检测的相关研究。

原文链接：

Blood-Epigenetic Biomarker Associations with Tumor Immunophenotype in Patients with Urothelial Carcinoma from JAVELIN Bladder 100