■替莫唑胺(TMZ)是治疗神经胶质瘤的关键组成部分。在常规临床实践中可以遇到TMZ引起的超突变,其重要性逐渐得到认可。然而,TMZ诱导的超突变与免疫反应之间的关系仍存在争议.
■我们介绍了一名38岁男性患者的病例,该患者接受了五次神经胶质瘤手术。最初诊断为IDH突变星形细胞瘤(WHO2级)在前两个手术,在随后的干预措施中,疾病进展至4级.在第四次手术之前,患者接受了3个周期的标准TMZ化疗和9个周期的剂量密集TMZ方案.在第四次手术中获得的肿瘤组织的基因组和免疫学分析显示了相对有利的免疫微环境,如免疫表型5所示,表明免疫疗法的潜在益处。因此,患者接受低剂量放疗联合免疫辅助治疗.完成4个周期的免疫治疗后,肿瘤明显缩小,导致部分反应。然而,经过6个月的反应,患者出现疾病进展。随后对第五次手术中获得的肿瘤组织进行分析,发现发生了超突变,突变特征分析将TMZ治疗归因于主要原因。不幸的是,病人不久后死亡,生存期为126个月。
■接受长期TMZ治疗方案的患者可能表现出更高的超突变易感性。TMZ诱导的这种超突变具有作为与神经胶质瘤中对免疫疗法的不利反应相关的指标的潜力。
UNASSIGNED: Temozolomide (TMZ) is a key component in the treatment of gliomas.
Hypermutation induced by TMZ can be encountered in routine clinical practice, and its significance is progressively gaining recognition. However, the relationship between TMZ-induced
hypermutation and the immunologic response remains controversial.
UNASSIGNED: We present the case of a 38-year-old male patient who underwent five surgeries for glioma. Initially diagnosed with IDH-mutant astrocytoma (WHO grade 2) during the first two surgeries, the disease progressed to grade 4 in subsequent interventions. Prior to the fourth surgery, the patient received 3 cycles of standard TMZ chemotherapy and 9 cycles of dose-dense TMZ regimens. Genomic and immunologic analyses of the tumor tissue obtained during the fourth surgery revealed a relatively favorable immune microenvironment, as indicated by an immunophenoscore of 5, suggesting potential benefits from immunotherapy. Consequently, the patient underwent low-dose irradiation combined with immunoadjuvant treatment. After completing 4 cycles of immunotherapy, the tumor significantly shrank, resulting in a partial response. However, after a 6-month duration of response, the patient experienced disease progression. Subsequent analysis of the tumor tissue obtained during the fifth surgery revealed the occurrence of
hypermutation, with mutation signature analysis attributing TMZ treatment as the primary cause. Unfortunately, the patient succumbed shortly thereafter, with a survival period of 126 months.
UNASSIGNED: Patients subjected to a prolonged regimen of TMZ treatment may exhibit heightened vulnerability to
hypermutation. This
hypermutation induced by TMZ holds the potential to function as an indicator associated with unfavorable response to immunotherapy in gliomas.