TTFields plus TMZ treatment effects on newly diagnosed Glioblastoma patients in peripheral blood. TTFields plus TMZ treatment effects on newly diagnosed Glioblastoma patients in peripheral blood

We report the application of single-cell-RNA-based sequencing technology for high-throughput profiling of peripheral blood mononuclear cells. By sequencing in total of 193,760 PBMCs in 12 GBM patients, we generated an overview of patient peripheral immune status with 38 biologically recongnized cell subtypes. By paired comparing pre- and post- treatment samples, we find a robust post-TTFields activation of adaptive immunity via the T1IFN trajectory anchored by plasmacytoid DCs. This study provides a framework for the application of scRNAseq towards characterization of peripheral immune activation status. Overall design: Examination of TTFields plus TMZ treatment effects in peripheral blood mononuclear cells. We collected PBMCs from 12 adult patients with newly diagnosed GBM after they have completed radiotherapy with concurrent TMZ. The first time point is at least 2 weeks after completion of chemoradiation and within 2 weeks before initiation of TTFields and TMZ. The second time point is approximately 4 weeks after initiation of TTFields and TMZ.

本研究报道了基于单细胞RNA测序（single-cell RNA sequencing, scRNAseq）技术对外周血单个核细胞（peripheral blood mononuclear cells, PBMCs）开展高通量表征分析的应用。本研究对12名胶质母细胞瘤（glioblastoma, GBM）患者共193760个PBMCs进行测序，基于38种经生物学确认的细胞亚型，绘制了患者外周免疫状态的全景图谱。通过配对比较治疗前与治疗后样本，本研究发现，在以浆细胞样树突状细胞（plasmacytoid dendritic cells, pDCs）锚定的I型干扰素（Type I Interferon, T1IFN）信号通路介导下，肿瘤电场治疗（Tumor Treating Fields, TTFields）后适应性免疫产生了显著激活。本研究为利用scRNAseq表征外周免疫激活状态提供了研究框架。

研究设计：分析肿瘤电场治疗联合替莫唑胺（temozolomide, TMZ）对外周血单个核细胞的作用效果。本研究从12名新诊断胶质母细胞瘤成年患者中采集PBMCs，这些患者已完成同步放化疗联合替莫唑胺治疗。首个采样时间点为放化疗结束后至少2周，且处于肿瘤电场治疗联合替莫唑胺启动前2周内；第二个采样时间点为肿瘤电场治疗联合替莫唑胺启动后约4周。