Several immunotherapy clinical trials in recurrent glioblastoma have reported long-term survival benefits in 10–20% of patients. Here we perform genomic analysis of tumor tissue from recurrent WHO grade IV glioblastoma patients acquired prior to immunotherapy intervention. We report that very low tumor mutation burden is associated with longer survival after recombinant polio virotherapy or after immune checkpoint blockade in recurrent glioblastoma patients. A relationship between tumor mutation burden and survival is not observed in cohorts of immunotherapy naïve newly diagnosed or recurrent glioblastoma patients. Transcriptomic analyses reveal an inverse relationship between tumor mutation burden and enrichment of inflammatory gene signatures in cohorts of recurrent, but not newly diagnosed glioblastoma tumors, implying that a relationship between tumor mutation burden and tumor-intrinsic inflammation evolves upon recurrence.

几项针对复发性胶质母细胞瘤的免疫疗法临床试验表明，长期生存获益在10％至20％的患者中。在这里，我们对免疫治疗干预之前获得的世卫组织IV级胶质母细胞瘤复发患者的肿瘤组织进行基因组分析。我们报告说，极低的肿瘤突变负担与重组脊髓灰质炎病毒疗法或复发性胶质母细胞瘤患者的免疫检查点封锁后的更长生存期相关。在新诊断或复发的胶质母细胞瘤患者中，未进行免疫治疗的人群中未观察到肿瘤突变负担与生存之间的关系。转录组学分析显示，在复发性但不是新诊断出的胶质母细胞瘤患者中，肿瘤突变负担与炎症基因标记的富集之间存在反比关系，