Lawler Sean E
Harvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, 4 Blackfan Circle, HIM 930A, Boston, MA, 02115, USA,
J Neurooncol. 2015 Jul;123(3):465-71. doi: 10.1007/s11060-015-1734-0. Epub 2015 Feb 15.
One of the more polarized ongoing debates in the brain tumor field over recent years has centered on the association of cytomegalovirus (CMV) with glioblastoma. Several laboratories have reported the presence of CMV antigens in glioblastoma patient specimens, whereas others have failed to detect them. CMV genomic DNA and mRNAs have been detected by PCR, but not in next-generation sequencing studies. CMV promotes high grade glioma progression in a mouse genetic model, and many CMV proteins promote cancer hallmarks in vitro, but actively replicating virus has not been isolated from tumor samples. A consensus is gradually emerging in which the presence of CMV antigens in glioblastoma is increasingly accepted. However, it remains challenging to understand this mechanistically due to the low levels of CMV nucleic acids and the absence of viral replication observed in tumors thus far. Nonetheless, these observations have inspired the development of novel therapeutic approaches based on anti-viral drugs and immunotherapy. The potential benefit of valganciclovir in glioblastoma has generated great interest, but efficacy remains to be established in a randomized trial. Also, early stage immunotherapy trials targeting CMV have shown promise. In the near future we will know more answers to these questions, and although areas of controversy may remain, and the mechanisms and roles of CMV in tumor growth are yet to be clearly defined, this widespread virus may have created important new therapeutic concepts and opportunities for the treatment of glioblastoma.
近年来,脑肿瘤领域中争议较大且仍在持续的一场辩论聚焦于巨细胞病毒(CMV)与胶质母细胞瘤的关联。多个实验室报告在胶质母细胞瘤患者标本中发现了CMV抗原,而其他实验室则未能检测到。通过聚合酶链反应(PCR)检测到了CMV基因组DNA和信使核糖核酸(mRNA),但在下一代测序研究中未检测到。在小鼠遗传模型中,CMV可促进高级别胶质瘤进展,且许多CMV蛋白在体外可促进癌症特征,但尚未从肿瘤样本中分离出活跃复制的病毒。一种共识正在逐渐形成,即越来越多人接受胶质母细胞瘤中存在CMV抗原这一观点。然而,由于CMV核酸水平较低且迄今在肿瘤中未观察到病毒复制,从机制上理解这一现象仍具有挑战性。尽管如此,这些观察结果激发了基于抗病毒药物和免疫疗法的新型治疗方法的开发。缬更昔洛韦在胶质母细胞瘤中的潜在益处引起了极大关注,但疗效仍有待在随机试验中确定。此外,针对CMV的早期免疫疗法试验已显示出前景。在不久的将来,我们将知晓这些问题的更多答案,尽管争议领域可能依然存在,且CMV在肿瘤生长中的机制和作用尚待明确界定,但这种广泛传播的病毒可能为胶质母细胞瘤的治疗创造了重要的新治疗理念和机会。