Abstract：
Pediatric low-grade gliomas (pLGGs) are the most common brain tumor types affecting children. Although gross-total resection remains the treatment of choice, many tumors are not amenable to complete removal, because they either involve midline structures, such as the optic chiasm or hypothalamus, and are not conducive to aggressive resection, or have diffuse biological features and blend with the surrounding brain. Historically, radiation therapy was used as the second-line option for disease control, but with the recognition that this often led to adverse long-term sequelae, particularly in young children, conventional chemotherapy assumed a greater role in initial therapy for unresectable tumors. A variety of agents demonstrated activity, but long-term disease control was suboptimal, with more than 50% of tumors exhibiting disease progression within 5 years. More recently, it has been recognized that a high percentage of these tumors in children exhibit constitutive activation of the mitogen-activated protein kinase (MAPK) pathway because of BRAF translocations or mutations, NFI mutations, or a host of other anomalies that converged on MAPK. This led to phase 1, 2, and 3 trials that explored the activity of blocking this signaling pathway, and the efficacy of this approach compared to conventional chemotherapy. Despite initial promise of these strategies, not all children tolerate this therapy, and many tumors resume growth once MAPK inhibition is stopped, raising concern that long-term and potentially life-long treatment will be required to maintain tumor control, even among responders. This observation has led to interest in other treatments, such as immunotherapy, that may delay or avoid the need for additional treatments. This chapter will summarize the place of immunotherapy in the current armamentarium for these tumors and discuss prior results and future options to improve disease control, with a focus on our prior efforts and experience in this field.
摘要：
小儿低度胶质瘤（pLGG）是影响儿童的最常见脑肿瘤类型。尽管全切仍是首选治疗方法，许多肿瘤无法完全切除，因为它们要么涉及中线结构，比如视神经交叉或下丘脑，不利于积极切除，或具有扩散的生物学特征并与周围的大脑融合。历史上,放射治疗被用作疾病控制的二线选择，但是认识到这通常会导致不利的长期后遗症，特别是在幼儿中，常规化疗在不可切除肿瘤的初始治疗中发挥更大的作用.各种药剂表现出活性，但长期的疾病控制并不理想,超过50%的肿瘤在5年内表现出疾病进展。最近,已经认识到，由于BRAF易位或突变，儿童中这些肿瘤的高百分比表现出丝裂原活化蛋白激酶（MAPK）途径的组成型激活，NFI突变,或许多其他在MAPK上汇聚的异常。这导致了第1、2和3期试验，探索了阻断这一信号通路的活性，与常规化疗相比，这种方法的疗效。尽管这些策略最初的承诺，不是所有的孩子都能忍受这种疗法,一旦MAPK抑制停止，许多肿瘤就会恢复生长，这引起了人们的关注，即需要长期和潜在的终身治疗来维持肿瘤控制，甚至在响应者中。这一观察结果引起了人们对其他治疗方法的兴趣，比如免疫疗法，这可能会延迟或避免需要额外的治疗。本章将总结免疫疗法在目前这些肿瘤的医疗设备中的地位，并讨论先前的结果和未来的选择，以改善疾病控制，重点介绍我们在这一领域的先前努力和经验。
