Yu Kenny K H, Basu Sreyashi, Baquer Gerard, Ahn Ryuhjin, Gantchev Jennifer, Jindal Sonali, Regan Michael S, Abou-Mrad Zaki, Prabhu Michael C, Williams Marc J, D'Souza Alicia D, Malinowski Seth W, Hopland Kelsey, Elhanati Yuval, Stopka Sylwia A, Stortchevoi Alexei, Couturier Charles, He Zhong, Sun Jingjing, Chen Yulong, Espejo Alexsandra B, Chow Kin Hoe, Yerrum Smitha, Kao Pei-Lun, Kerrigan Brittany Parker, Norberg Lisa, Nielsen Douglas, Puduvalli Vinay K, Huse Jason, Beroukhim Rameen, Kim Betty Y S, Goswami Sangeeta, Boire Adrienne, Frisken Sarah, Cima Michael J, Holdhoff Matthias, Lucas Calixto-Hope G, Bettegowda Chetan, Levine Stuart S, Bale Tejus A, Brennan Cameron, Reardon David A, Lang Frederick F, Chiocca E Antonio, Ligon Keith L, White Forest M, Sharma Padmanee, Tabar Viviane, Agar Nathalie Y R
Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Immunotherapy Platform and James P. Allison Institute, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Nat Commun. 2025 Apr 28;16(1):3957. doi: 10.1038/s41467-025-58452-8.
Glioblastoma (GBM) is an aggressive primary brain cancer with few effective therapies. Stereotactic needle biopsies are routinely used for diagnosis; however, the feasibility and utility of investigative biopsies to monitor treatment response remains ill-defined. Here, we demonstrate the depth of data generation possible from routine stereotactic needle core biopsies and perform highly resolved multi-omics analyses, including single-cell RNA sequencing, spatial transcriptomics, metabolomics, proteomics, phosphoproteomics, T-cell clonotype analysis, and MHC Class I immunopeptidomics on standard biopsy tissue obtained intra-operatively. We also examine biopsies taken from different locations and provide a framework for measuring spatial and genomic heterogeneity. Finally, we investigate the utility of stereotactic biopsies as a method for generating patient-derived xenograft (PDX) models. Multimodal dataset integration highlights spatially mapped immune cell-associated metabolic pathways and validates inferred cell-cell ligand-receptor interactions. In conclusion, investigative biopsies provide data-rich insight into disease processes and may be useful in evaluating treatment responses.
胶质母细胞瘤（GBM）是一种侵袭性原发性脑癌，有效治疗方法很少。立体定向针吸活检通常用于诊断；然而，用于监测治疗反应的研究性活检的可行性和实用性仍不明确。在此，我们展示了常规立体定向针芯活检可能产生的数据深度，并对术中获取的标准活检组织进行了高分辨率多组学分析，包括单细胞RNA测序、空间转录组学、代谢组学、蛋白质组学、磷酸蛋白质组学、T细胞克隆型分析和MHC I类免疫肽组学。我们还检查了从不同位置采集的活检样本，并提供了一个测量空间和基因组异质性的框架。最后，我们研究了立体定向活检作为生成患者来源异种移植（PDX）模型的方法的实用性。多模态数据集整合突出了空间映射的免疫细胞相关代谢途径，并验证了推断的细胞间配体-受体相互作用。总之，研究性活检为疾病过程提供了丰富的数据洞察，可能有助于评估治疗反应。
