Single-cell and Bulk Transcriptomic Profiling of Anti-PCSK9-Armed Oncolytic Virus Therapy Reveals MHC-I Rewiring and Durable CD8 T Cell Immunity in Colorectal Cancer

Sequencing datasets were generated using single-cell transcriptomic profiling and bulk transcriptomic sequencing (bulk RNA-seq) to characterize tumor and immune responses to oncolytic virus (OV) therapy in colorectal cancer models. Tumors treated with oncolytic VSVDelta51, PCSK9 inhibition, the combination regimen, and matched controls were collected to evaluate OV-driven alterations in antigen presentation and T cell signaling within the tumor microenvironment at single-cell resolution, while bulk RNA-seq provided complementary tissue-level transcriptional changes and support for key pathway and antigen-presentation programs. The study investigates OV-induced PCSK9 upregulation and MHC-I modulation across malignant and bystander cell populations, and quantifies associated shifts in tumor-infiltrating T cell states, clonal and functional programs, and features of immune memory inferred from single-cell profiles, with bulk analyses corroborating treatment-associated remodeling of antigen-processing and immune activation signatures at the tissue level.

本数据集通过单细胞转录组测序（single-cell transcriptomic profiling）与体转录组测序（bulk transcriptomic sequencing，即bulk RNA-seq）生成，用于解析结直肠癌模型中肿瘤与免疫对溶瘤病毒（oncolytic virus, OV）治疗的应答特征。研究收集了经溶瘤VSVDelta51、PCSK9抑制疗法、联合治疗方案处理的肿瘤样本及匹配对照样本，以单细胞分辨率评估溶瘤病毒驱动的肿瘤微环境内抗原呈递与T细胞信号通路改变；同时通过体RNA-seq获取互补的组织水平转录组变化数据，为关键通路与抗原呈递程序提供佐证。本研究探究了溶瘤病毒诱导的恶性细胞及旁观者细胞群中的PCSK9上调与MHC-I分子调控现象，量化肿瘤浸润T细胞状态、克隆与功能程序的相关变化，以及从单细胞谱推断的免疫记忆特征；体转录组分析则验证了治疗相关的组织水平抗原加工与免疫激活特征重塑。