斯坦福大学医学院Michael Angelo小组的一项最新研究揭示了人类胶质瘤从诊断到治疗和复发的多组学研究。2025年12月11日出版的《癌细胞》发表了这项成果。

为了揭示治疗逃逸和肿瘤微环境（TME）景观的特征，研究组应用空间蛋白质组学、转录组学和糖组学对310名成人和儿童患者的670个病变进行了研究。单细胞分析显示，B7H3+肿瘤细胞在胶质母细胞瘤（GBM）和多形性黄色星形细胞瘤中的患病率很高，而大多数胶质瘤，包括儿科病例，在不到50%的肿瘤细胞中表达可靶向的肿瘤抗原，这可能解释了试验失败的原因。

异柠檬酸脱氢酶（IDH）突变胶质瘤的成对样本揭示了肿瘤免疫空间重组驱动的复发，从T细胞和血管相关的骨髓细胞富集壁龛转移到小胶质细胞和CD206⁺巨噬细胞主导的肿瘤。多组学整合鉴定N -糖基化是最好的分级器，而免疫转录组最能预测GBM的生存。作为一项社区抵抗，这项研究为胶质瘤的靶向、分类、结果预测和所有阶段TME组成的基线提供了一个框架。

研究人员表示，胶质瘤是最致命的癌症之一，治疗选择有限。

附：英文原文

Title: Multi-omic landscape of human gliomas from diagnosis to treatment and recurrence

Author: Hadeesha Piyadasa, Benjamin Oberlton, Mikaela Ribi, Ke Leow, Jolene S. Ranek, Inna Averbukh, Meelad Amouzgar, Candace C. Liu, Davide G. Franchina, Noah F. Greenwald, Erin F. McCaffrey, Rashmi Kumar, Selena Ferrian, Albert G. Tsai, Ferda Filiz, Christine Camacho Fullaway, Marc Bosse, Sricharan Reddy Varra, Alex Kong, Cameron Sowers, Melanie Hayden Gephart, Pablo Nuez-Perez, EnJun Yang, Mike Travers, Michael J. Schachter, Samantha Liang, Maria R. Santi, Samantha Bucktrout, Pier Federico Gherardini, John Connolly, Kristina Cole, Michael E. Barish, Christine E. Brown, Derek A. Oldridge, Richard R. Drake, Joanna J. Phillips, Hideho Okada, Robert Prins, Sean C. Bendall, Michael Angelo

Issue&Volume: 2025-12-11

Abstract: Gliomas are among the most lethal cancers, with limited treatment options. To uncover hallmarks of therapeutic escape and tumor microenvironment (TME) landscape, we applied spatial proteomics, transcriptomics, and glycomics to 670 lesions from 310 adult and pediatric patients. Single-cell analysis shows high B7H3+ tumor cell prevalence in glioblastoma (GBM) and pleomorphic xanthoastrocytoma, while most gliomas, including pediatric cases, express targetable tumor antigens in less than 50% of tumor cells, potentially explaining trial failures. Paired samples of isocitrate dehydrogenase (IDH)-mutant gliomas reveal recurrence driven by tumor-immune spatial reorganization, shifting from T cell and vasculature-associated myeloid cell-enriched niches to microglia and CD206+ macrophage-dominated tumors. Multi-omic integration identified N-glycosylation as the best classifier of grade, while the immune transcriptome best predicted GBM survival. Provided as a community resource, this study offers a framework for glioma targeting, classification, outcome prediction, and a baseline of TME composition across all stages.

DOI: 10.1016/j.ccell.2025.11.006

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(25)00499-4