The Brown Center for Immunotherapy, Department of Medicine, Melvin and Bren Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Oncogene. 2023 Jun;42(27):2155-2165. doi: 10.1038/s41388-023-02738-y. Epub 2023 Jun 5.
Glioblastoma (GBM) is one of the deadliest types of cancer and highly refractory to chemoradiation and immunotherapy. One of the main reasons for this resistance to therapy lies within the heterogeneity of the tumor and its associated microenvironment. The vast diversity of cell states, composition of cells, and phenotypical characteristics makes it difficult to accurately classify GBM into distinct subtypes and find effective therapies. The advancement of sequencing technologies in recent years has further corroborated the heterogeneity of GBM at the single cell level. Recent studies have only begun to elucidate the different cell states present in GBM and how they correlate with sensitivity to therapy. Furthermore, it has become clear that GBM heterogeneity not only depends on intrinsic factors but also strongly differs between new and recurrent GBM, and treatment naïve and experienced patients. Understanding and connecting the complex cellular network that underlies GBM heterogeneity will be indispensable in finding new ways to tackle this deadly disease. Here, we present an overview of the multiple layers of GBM heterogeneity and discuss novel findings in the age of single cell technologies.
胶质母细胞瘤(GBM)是最致命的癌症类型之一,对放化疗和免疫疗法高度耐受。这种治疗耐药性的主要原因之一在于肿瘤及其相关微环境的异质性。细胞状态、细胞组成和表型特征的巨大多样性使得准确地将 GBM 分为不同的亚型并找到有效的治疗方法变得困难。近年来测序技术的进步进一步证实了 GBM 在单细胞水平上的异质性。最近的研究才刚刚开始阐明 GBM 中存在的不同细胞状态以及它们与对治疗的敏感性的相关性。此外,很明显,GBM 异质性不仅取决于内在因素,而且在新的和复发性 GBM 之间、在治疗初治和经验丰富的患者之间也有很大的不同。了解和连接构成 GBM 异质性基础的复杂细胞网络,对于寻找新的方法来攻克这种致命疾病是必不可少的。在这里,我们概述了 GBM 异质性的多个层次,并讨论了单细胞技术时代的新发现。