北京大学白凡课题组在研究中取得进展。他们提出了单细胞分辨率的泛癌人脑转移图谱。相关论文于2025年4月10日发表在《癌细胞》杂志上。

研究人员对108个BrM样本和111个原发肿瘤（PTs）样本进行了综合单细胞RNA测序分析，以研究癌症谱系和亚群中细胞状态和组成的特征和重塑。恶性细胞复发和富集的特征是染色体不稳定性增加，明显的增殖和血管生成特征，并采用神经样BrM相关的元程序。免疫抑制的骨髓和间质亚群在BrM肿瘤微环境中占主导地位，这与预后不良和免疫治疗耐药有关。

此外，鉴定出五种不同的BrM生态型，与特定的组织病理学模式和临床特征相关。这项工作定义了跨癌症类型的BrM生物学特征，并表明可能存在共同的依赖性，这可能在临床上被利用。

研究人员表示，脑转移瘤（BrMs）仍然是转移性癌症患者的主要临床和治疗挑战。然而，他们对BrM理解的进展受到BrM分析研究的样本量和分辨率的限制。

附：英文原文

Title: Pan-cancer human brain metastases atlas at single-cell resolution

Author: Xudong Xing, Jian Zhong, Jana Biermann, Hao Duan, Xinyu Zhang, Yu Shi, Yixin Gao, Kejun He, Duanyang Zhai, Feng Luo, Yanxing Lai, Feizhe Xiao, Wenying Wang, Mengru Wang, Jianguo Xu, Hao Liu, Jiaze Tang, Liangzhao Chu, Tunan Chen, Edridge K. D’Souza, Lindsay Caprio, Leon Ebel, Devanik Biswas, Azzurra Cottarelli, Yonggao Mou, Benjamin Izar, Nu Zhang, Fan Bai

Issue&Volume: 2025-04-10

Abstract: Brain metastases (BrMs) remain a major clinical and therapeutic challenge in patients with metastatic cancers. However, advances in our understanding of BrM have been hampered by the constrained sample size and resolution of BrM profiling studies. Here, we perform integrative single-cell RNA sequencing analysis on 108 BrM samples and 111 primary tumor (PTs) samples to investigate the characteristics and remodeling of cell states and composition across cancer lineages and subsets. Recurring and enriched features of malignant cells are increased chromosomal instability, marked proliferative and angiogenic hallmarks, and adoption of a neural-like BrM-associated metaprogram. Immunosuppressive myeloid and stromal subsets dominate the BrM tumor microenvironment, which are associated with poor prognosis and resistance to immunotherapy. Furthermore, five distinct BrM ecotypes are identified, correlating with specific histopathological patterns and clinical characteristics. This work defines hallmarks of BrM biology across cancer types and suggests that shared dependencies may exist, which may be exploited clinically.

DOI: 10.1016/j.ccell.2025.03.025

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(25)00126-6