肿瘤细胞治疗研究
英文原题：The critical role of the endogenous immune compartment after CAR T cell therapy in recurrent GBM.
这些发现表明，宿主免疫细胞在 GBM 的 CAR-T 细胞治疗中发挥关键作用，提示调节内源性免疫组分的联合策略可改进下一代治疗。
胶质母细胞瘤（GBM）是成人最常见的原发性恶性脑肿瘤，中位生存期不足15个月，复发后尚无有效治疗。近期一项针对复发性 GBM 的脑室内双靶点嵌合抗原受体（CAR）T 细胞 I 期试验（ClinicalTrials.gov 注册号：NCT05168423）显示出有希望的应答，包括肿瘤缩小和生存期延长，但复发仍很常见。我们对应答者和未应答者的纵向脑脊液（CSF）及肿瘤样本进行了深入分析，以刻画输注后的免疫动态。研究发现，虽然所有患者输注后的 CAR-T 细胞均被激活，但临床结局取决于内源性免疫图谱的不同重塑。应答者的特征是细胞毒性 NK 细胞扩增；未应答者则表现为调节性 T 细胞扩增，以及基线时免疫抑制性清道夫型髓系细胞丰富。这些发现表明，宿主免疫细胞在 GBM CAR-T 治疗中发挥关键作用，提示调节内源性免疫细胞群的联合策略可能改善下一代疗法。
Glioblastoma (GBM) is the most common primary malignant brain tumor in adults, with a median survival of under 15 months and no effective treatment after recurrence. A recent phase 1 trial of intracerebroventricular bivalent chimeric antigen receptor (CAR) T cells in recurrent GBM, registered at ClinicalTrials.gov (NCT05168423), showed promising responses, including tumor reduction and prolonged survival. However, relapse remains common. We performed in-depth profiling of longitudinal cerebrospinal fluid (CSF) and tumor samples from responders and non-responders to characterize immune dynamics following infusion. Our study reveals that, although CAR T cells activate post infusion across all patients, outcomes were defined by divergent remodeling of the endogenous immune landscape. Cytotoxic natural killer cell expansion characterized responders, whereas regulatory T cell expansion and abundant baseline immunosuppressive scavenger myeloid cells characterized non-responders. These findings indicate that host immune cells play a critical role in CAR T cell therapy for GBM, suggesting that combinatorial strategies modulating the endogenous immune compartment could improve next-generation treatments.
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