Ladomersky Erik, Zhai Lijie, Gritsina Galina, Genet Matthew, Lauing Kristen L, Wu Meijing, James C David, Wainwright Derek A
Department of Neurological Surgery, USA.
Department of Neurological Surgery, USA; Department of Biochemistry and Molecular Genetics, USA; Northwestern Brain Tumor Institute,USA; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL 60611, USA.
Neurosci Lett. 2016 Sep 6;630:203-208. doi: 10.1016/j.neulet.2016.08.002. Epub 2016 Aug 1.
Glioblastoma (GBM) is the most common primary malignant brain tumor in adults, with an average age of 64 years at the time of diagnosis. To study GBM, a number of mouse brain tumor models have been utilized. In these animal models, subjects tend to range from 6 to 12 weeks of age, which is analogous to that of a human teenager. Here, we examined the impact of age on host immunity and the gene expression associated with immune evasion in immunocompetent mice engrafted with syngeneic intracranial GL261. The data indicate that, in mice with brain tumors, youth conveys an advantage to survival. While age did not affect the tumor-infiltrating T cell phenotype or quantity, we discovered that old mice express higher levels of the immunoevasion enzyme, IDO1, which was decreased by the presence of brain tumor. Interestingly, other genes associated with promoting immunosuppression including CTLA-4, PD-L1 and FoxP3, were unaffected by age. These data highlight the possibility that IDO1 contributes to faster GBM outgrowth with advanced age, providing rationale for future investigation into immunotherapeutic targeting in the future.
胶质母细胞瘤(GBM)是成人中最常见的原发性恶性脑肿瘤,诊断时的平均年龄为64岁。为了研究GBM,已经使用了多种小鼠脑肿瘤模型。在这些动物模型中,实验对象的年龄通常在6至12周之间,这相当于人类青少年的年龄。在此,我们研究了年龄对宿主免疫以及与免疫逃逸相关的基因表达的影响,这些实验对象是接种了同基因颅内GL261的具有免疫活性的小鼠。数据表明,在患有脑肿瘤的小鼠中,年轻对生存具有优势。虽然年龄并未影响肿瘤浸润性T细胞的表型或数量,但我们发现老年小鼠表达更高水平的免疫逃逸酶IDO1,而脑肿瘤的存在会使其表达降低。有趣的是,其他与促进免疫抑制相关的基因,包括CTLA-4、PD-L1和FoxP3,不受年龄影响。这些数据凸显了IDO1可能导致GBM随着年龄增长而更快生长的可能性,为未来针对免疫治疗靶点的研究提供了理论依据。