Departmenlt of Oncology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China.
Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, Shandong Province, China.
Cell Death Dis. 2021 Mar 19;12(4):299. doi: 10.1038/s41419-021-03568-0.
Glioblastoma (GB) is the most common high-grade intracranial malignant tumor with highly malignant biological behavior and a high recurrence rate. Although anti-PD-1/PD-L1 antibodies have achieved significant survival benefits in several kinds of solid tumors, the phase III clinical trial Checkmate 143 demonstrated that nivolumab, which targets PD-1, did not achieve survival benefits compared with bevacizumab in recurrent glioblastoma (rGB) patients. Nevertheless, neoadjuvant anti-PD-1 therapy followed by surgery and adjuvant anti-PD-1 therapy could effectively activate local and systemic immune responses and significantly improve the OS of rGB patients. Furthermore, several studies have also confirmed the progress made in applying tumor-specific peptide vaccination or chimeric antigen receptor-T (CAR-T) cell therapy to treat rGB patients, and successes with antibodies targeting other inhibitory checkpoints or costimulatory molecules have also been reported. These successes inspired us to explore candidate combination treatments based on anti-PD-1/PD-L1 antibodies. However, effective predictive biomarkers for clinical efficacy are urgently needed to avoid economic waste and treatment delay. Attempts to prolong the CAR-T cell lifespan and increase T cell infiltration through engineering techniques are addressing the challenge of strengthening T cell function. In this review, we describe the immunosuppressive molecular characteristics of rGB; clinical trials exploring anti-PD-1/PD-L1 therapy, tumor-specific peptide vaccination, and CAR-T cell therapy; candidate combination strategies; and issues related to strengthening T cell function.
胶质母细胞瘤（GB）是最常见的高级颅内恶性肿瘤，具有高度恶性的生物学行为和高复发率。尽管抗 PD-1/PD-L1 抗体在几种实体肿瘤中取得了显著的生存获益，但 Checkmate 143 期临床试验表明，针对 PD-1 的纳武单抗在复发性胶质母细胞瘤（rGB）患者中并未比贝伐珠单抗获得生存获益。然而，新辅助抗 PD-1 治疗后手术和辅助抗 PD-1 治疗可以有效激活局部和全身免疫反应，显著改善 rGB 患者的总生存期。此外，几项研究还证实了在治疗 rGB 患者方面应用肿瘤特异性肽疫苗或嵌合抗原受体-T（CAR-T）细胞治疗取得的进展，并且针对其他抑制性检查点或共刺激分子的抗体也取得了成功。这些成功促使我们探索基于抗 PD-1/PD-L1 抗体的候选联合治疗方法。然而，迫切需要有效的预测生物标志物来评估临床疗效，以避免经济浪费和治疗延误。通过工程技术延长 CAR-T 细胞寿命并增加 T 细胞浸润的尝试正在解决增强 T 细胞功能的挑战。在这篇综述中，我们描述了 rGB 的免疫抑制分子特征；探索抗 PD-1/PD-L1 治疗、肿瘤特异性肽疫苗接种和 CAR-T 细胞治疗的临床试验；候选联合策略；以及与增强 T 细胞功能相关的问题。
