德国法兰克福癌症研究所Katharina Imkeller团队的研究认为空间免疫分析定义了具有功能性三级淋巴结构的人类胶质瘤的一个亚群。这一研究成果发表在2025年10月21日出版的国际学术期刊《免疫学》上。

该研究团队研究了胶质瘤肿瘤内三级淋巴结构（TLSs）的特征和临床相关性，这些结构以空间转录组和蛋白质组分析为主题。在642例胶质瘤队列中，15%的肿瘤存在TLSs，并与血管周围空间重构和细胞外基质成分的空间再分布有关。基于不同的细胞组成和免疫活性，可以定义三种不同的TLS亚型。虽然所有亚型都缺乏经典的生发中心结构，但某些TLSs表现出动态免疫功能的特征，包括克隆T细胞和B细胞扩增、IgA⁺和IgG⁺浆细胞生成，以及树突状细胞- T细胞相互作用。具有主动免疫应答特征的TLSs的存在与总生存率的提高相关。因此，在一些胶质瘤中可以检测到功能性适应性免疫反应，这意味着分层和治疗。

据介绍，成人型分化主题胶质瘤是最常见的原发性脑肿瘤，对免疫治疗反应不佳，被认为是免疫“冷”肿瘤。

附：英文原文

Title: Spatial immune profiling defines a subset of human gliomas with functional tertiary lymphoid structures

Author: Pinar Cakmak, Jennifer H. Lun, Aakanksha Singh, Jadranka Macas, Jonathan Schupp, Jonas Schuck, Zeina Mahmoud, Miriam Khler, Tatjana Starzetz, Michael C. Burger, Eike Steidl, Lucie Marie Hasse, Elke Hattingen, Karl H. Plate, Yvonne Reiss, Katharina Imkeller

Issue&Volume: 2025-10-21

Abstract: Adult-type diffuse gliomas, the most common primary brain tumors, respond poorly to immune-based therapies and are considered immunologically “cold” tumors. Here, we examined the features and clinical relevance of glioma intratumoral tertiary lymphoid structures (TLSs) using spatial transcriptome and proteome profiling. In a cohort of 642 gliomas, TLSs were present in 15% of tumors and associated with a remodeled perivascular space and spatial redistribution of extracellular matrix components. Three distinct TLS subtypes could be defined based on differing cellular composition and immune activity. While all subtypes lacked classical germinal center architecture, certain TLSs exhibited features of dynamic immune functions, including clonal T and B cell expansion, generation of IgA+ and IgG+ plasma cells, and dendritic cell-T cell interactions. The presence of TLSs with active immune response features correlated with improved overall survival. Thus, a functional adaptive immune response is detectable in some gliomas, with implications for stratification and treatment.

DOI: 10.1016/j.immuni.2025.09.018

Source: https://www.cell.com/immunity/abstract/S1074-7613(25)00429-7