中枢神经系统（CNS）WHO 2级低级别胶质瘤（LGG）患者由于对高级别胶质瘤的治疗耐药和恶变，复发风险高，长期预后不良。考虑到LGG患者相对完整的全身免疫力和缓慢生长的特性，免疫疗法可能为LGG患者提供有效的治疗选择。我们进行了一项前瞻性、随机预研究，以评估激动性抗CD27多肽IMA950疫苗的安全性和免疫学反应抗体，varlilumab，用于 CNS WHO 2 级 LGG 患者。患者在术前随机接受 IMA950 Poly-ICLC 和 Varlilumab（第 1 组）或 IMA950 Poly-ICLC（第 2 组）联合治疗，随后接受佐剂疫苗。共有 14 名符合条件的患者参加了该研究。四名患者接受了手术前疫苗，但由于切除肿瘤的高级别诊断而被排除在手术后疫苗之外。没有观察到治疗方案限制性毒性。所有患者在接种疫苗后外周血中抗 IMA950 CD8 T 细胞反应均显着增加，但在切除的肿瘤中未检测到 IMA950 反应性 CD8 T 细胞。质谱流式分析显示，添加 Varlilumab 促进了 PBMC 中的 1 型辅助性 T 效应记忆 CD4 和效应记忆 CD8 T 细胞分化，但在肿瘤微环境中则不然。包括 Varlilumab 在内的联合免疫疗法具有良好的耐受性，并诱导疫苗反应性 T 细胞分化。 -细胞在外周血中扩增，但在肿瘤中没有可检测到的反应。有必要进一步开发克服血液肿瘤屏障的策略，以提高 LGG 患者免疫治疗的疗效。© 作者 2023。由牛津大学出版社代表神经肿瘤学会出版。版权所有。如需权限，请发送电子邮件至：journals.permissions@oup.com。

Central nervous system (CNS) WHO grade 2 low-grade glioma (LGG) patients are at high risk for recurrence and with unfavorable long-term prognosis due to the treatment resistance and malignant transformation to high-grade glioma. Considering the relatively intact systemic immunity and slow-growing nature, immunotherapy may offer an effective treatment option for LGG patients.We conducted a prospective, randomized pilot study to evaluate the safety and immunological response of the multi-peptide IMA950 vaccine with agonistic anti-CD27 antibody, varlilumab, in CNS WHO grade 2 LGG patients. Patients were randomized to receive combination therapy with IMA950+poly-ICLC and varlilumab (Arm 1) or IMA950+poly-ICLC (Arm 2) before surgery, followed by adjuvant vaccines.A total of 14 eligible patients were enrolled in the study. Four patients received pre-surgery vaccines but were excluded from post-surgery vaccines due to the high-grade diagnosis of the resected tumor. No regimen-limiting toxicity was observed. All patients demonstrated a significant increase of anti-IMA950 CD8 + T-cell response post-vaccine in the peripheral blood, but no IMA950-reactive CD8 + T-cells were detected in the resected tumor. Mass cytometry analyses revealed that adding varlilumab promoted T helper type 1 effector memory CD4 + and effector memory CD8 + T-cell differentiation in the PBMC but not in the tumor microenvironment.The combinational immunotherapy, including varlilumab, was well-tolerated and induced vaccine-reactive T-cell expansion in the peripheral blood but without a detectable response in the tumor. Further developments of strategies to overcome the blood-tumor barrier are warranted to improve the efficacy of immunotherapy for LGG patients.© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.