Zhuo Shenghua, Yang Shuo, Chen Shenbo, Ding Yueju, Cheng Honglei, Yang Liangwang, Wang Kai, Yang Kun
Department of Neurosurgery, the First Affiliated Hospital of Hainan Medical University (Hainan Academy of Medical Sciences), Haikou, China.
International Center for Aging and Cancer, Hainan Medical University (Hainan Academy of Medical Sciences), Haikou, China.
Discov Oncol. 2024 Oct 29;15(1):602. doi: 10.1007/s12672-024-01449-4.
Glioma has a poor prognosis, which is attributable to its inherent characteristics and lack of specific treatments. Immunotherapy plays a pivotal role in the contemporary management of malignancies. Despite the initiation of numerous immunotherapy-based clinical trials, their effects on enhancing glioma prognosis remain limited, highlighting the need for innovative and effective therapeutic targets and strategies to address this challenge. Since the 1990s, there has been a growing interest in cancer-testis antigens (CTAs) present in normal mammalian testicular germ cells and placental trophoblast cells, which exhibit reactivated expression in various tumor types. Mechanisms such as DNA methylation, histone modification, transcriptional regulation, and alternative splicing influence the expression of CTAs in tumors. The distinct expression patterns and robust immunogenicity of CTAs are promising tumor biomarkers and optimal targets for immunotherapy. Previous reports have shown that multiple CTAs are present in gliomas and are closely related to prognosis. The expression of these antigens is also associated with the immune response in gliomas and the effectiveness of immunotherapy. Significantly, numerous clinical trials, with IL13RA2 as a representative CTA member, have assessed the immunotherapeutic potential of gliomas and have shown favorable clinical efficacy. This review provides a comprehensive overview of the regulation and function of CTAs, summarizes their expression and role in gliomas, emphasizes their importance as immunotherapy targets in gliomas, and discusses related challenges and future interventions.
胶质瘤预后较差，这归因于其固有特征以及缺乏特异性治疗方法。免疫疗法在当代恶性肿瘤治疗中发挥着关键作用。尽管开展了众多基于免疫疗法的临床试验，但其对改善胶质瘤预后的效果仍然有限，这凸显了需要创新且有效的治疗靶点和策略来应对这一挑战。自20世纪90年代以来，人们对正常哺乳动物睾丸生殖细胞和胎盘滋养层细胞中存在的癌胚抗原（CTAs）的兴趣日益浓厚，这些抗原在各种肿瘤类型中呈现重新激活的表达。DNA甲基化、组蛋白修饰、转录调控和可变剪接等机制影响CTAs在肿瘤中的表达。CTAs独特的表达模式和强大的免疫原性使其成为有前景的肿瘤生物标志物和免疫治疗的理想靶点。先前的报道表明，胶质瘤中存在多种CTAs，且与预后密切相关。这些抗原的表达还与胶质瘤中的免疫反应及免疫治疗效果相关。值得注意的是，以IL13RA2作为CTA代表性成员的众多临床试验评估了胶质瘤的免疫治疗潜力，并显示出良好的临床疗效。本综述全面概述了CTAs的调控和功能，总结了它们在胶质瘤中的表达及作用，强调了它们作为胶质瘤免疫治疗靶点的重要性，并讨论了相关挑战和未来干预措施。
