Department of Neurosurgery, Peking University Third Hospital, Peking University, Beijing, China.
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Front Immunol. 2024 Apr 4;15:1369972. doi: 10.3389/fimmu.2024.1369972. eCollection 2024.
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.
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.
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.
替莫唑胺（TMZ）是治疗神经胶质瘤的重要组成部分。在常规临床实践中可以遇到 TMZ 诱导的超突变，其意义逐渐得到认可。然而，TMZ 诱导的超突变与免疫反应之间的关系仍存在争议。
我们报告了一名 38 岁男性患者的病例，他因神经胶质瘤接受了 5 次手术。前两次手术最初诊断为 IDH 突变型星形细胞瘤（WHO 分级 2 级），随后疾病在后续干预中进展为 4 级。第四次手术前，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。第四次手术获得的肿瘤组织的基因组和免疫分析显示出相对有利的免疫微环境，免疫表型评分为 5，提示免疫治疗可能有益。因此，患者接受了低剂量放疗联合免疫佐剂治疗。完成 4 个周期的免疫治疗后，肿瘤明显缩小，部分缓解。然而，在 6 个月的缓解期后，患者出现疾病进展。第五次手术获得的肿瘤组织分析显示发生了超突变，突变特征分析将 TMZ 治疗归因于主要原因。不幸的是，患者随后去世，生存时间为 126 个月。
接受长时间 TMZ 治疗的患者可能更容易发生超突变。这种 TMZ 诱导的超突变可能成为神经胶质瘤免疫治疗反应不良的相关指标。
