University of Florida Brain Tumor Immunotherapy Program, Preston A. Wells, Jr. Center for Brain Tumor Therapy, Lillian S. Wells Department of Neurosurgery, McKnight Brain Institute, University of Florida, Gainesville, Florida, USA.
Division of Neuro-Oncology, Department of Neurological Surgery and Neurology, USC Keck Brain Tumor Center, University of Southern California Keck School of Medicine, Los Angeles, California, USA.
Neuro Oncol. 2024 Nov 4;26(11):1964-1980. doi: 10.1093/neuonc/noae131.
Brain tumors, particularly glioblastoma (GBM), are devastating and challenging to treat, with a low 5-year survival rate of only 6.6%. Mouse models are established to understand tumorigenesis and develop new therapeutic strategies. Large-scale genomic studies have facilitated the identification of genetic alterations driving human brain tumor development and progression. Genetically engineered mouse models (GEMMs) with clinically relevant genetic alterations are widely used to investigate tumor origin. Additionally, syngeneic implantation models, utilizing cell lines derived from GEMMs or other sources, are popular for their consistent and relatively short latency period, addressing various brain cancer research questions. In recent years, the success of immunotherapy in specific cancer types has led to a surge in cancer immunology-related research which specifically necessitates the utilization of immunocompetent mouse models. In this review, we provide a comprehensive summary of GEMMs and syngeneic mouse models for adult brain tumors, emphasizing key features such as model origin, genetic alteration background, oncogenic mechanisms, and immune-related characteristics. Our review serves as a valuable resource for the brain tumor research community, aiding in the selection of appropriate models to study cancer immunology.
脑肿瘤,尤其是胶质母细胞瘤(GBM),具有破坏性且难以治疗,其 5 年生存率仅为 6.6%。建立小鼠模型是为了了解肿瘤发生机制并开发新的治疗策略。大规模基因组研究促进了鉴定驱动人类脑肿瘤发生和发展的遗传改变。具有临床相关遗传改变的基因工程小鼠模型(GEMMs)广泛用于研究肿瘤起源。此外,利用源自 GEMMs 或其他来源的细胞系的同源移植模型因其稳定且潜伏期相对较短而受到欢迎,可用于解决各种脑癌研究问题。近年来,免疫疗法在特定癌症类型中的成功导致了癌症免疫学相关研究的激增,这特别需要使用免疫活性小鼠模型。在这篇综述中,我们全面总结了用于成人脑肿瘤的 GEMMs 和同源移植小鼠模型,强调了模型起源、遗传改变背景、致癌机制和免疫相关特征等关键特征。我们的综述为脑肿瘤研究界提供了有价值的资源,有助于选择合适的模型来研究癌症免疫学。