Co-expression of immune checkpoints in glioblastoma revealed by single-nucleus RNA sequencing and spatial transcriptomics

Dingyi Yuan; Wenting Chen; Shasha Jin; Wei Li; Wanmei Liu; Liu Liu; Yinhao Wu; Yuxin Zhang; Xiaoyu He; Jingwei Jiang; Hongbin Sun; Xiangyu Liu; Jun Liu

doi:10.1016/j.csbj.2024.04.014

Co-expression of immune checkpoints in glioblastoma revealed by single-nucleus RNA sequencing and spatial transcriptomics

Comput Struct Biotechnol J. 2024 Apr 10:23:1534-1546. doi: 10.1016/j.csbj.2024.04.014. eCollection 2024 Dec.

Authors

Dingyi Yuan¹, Wenting Chen¹, Shasha Jin¹, Wei Li², Wanmei Liu¹, Liu Liu³, Yinhao Wu¹, Yuxin Zhang¹, Xiaoyu He¹, Jingwei Jiang¹, Hongbin Sun³, Xiangyu Liu², Jun Liu¹

Affiliations

¹ New Drug Screening and Pharmacodynamics Evaluation Center, China Pharmaceutical University, Nanjing, China.
² Department of Neurosurgery, the Affiliated Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, China.
³ Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, China Pharmaceutical University, Nanjing, China.

Abstract

Glioblastoma (GBM) is one of the most malignant tumors of the central nervous system. The pattern of immune checkpoint expression in GBM remains largely unknown. We performed snRNA-Seq and spatial transcriptomic (ST) analyses on untreated GBM samples. 8 major cell types were found in both tumor and adjacent normal tissues, with variations in infiltration grade. Neoplastic cells_6 was identified in malignant cells with high expression of invasion and proliferator-related genes, and analyzed its interactions with microglia, MDM cells and T cells. Significant alterations in ligand-receptor interactions were observed, particularly between Neoplastic cells_6 and microglia, and found prominent expression of VISTA/VSIG3, suggesting a potential mechanism for evading immune system attacks. High expression of TIM-3, VISTA, PSGL-1 and VSIG-3 with similar expression patterns in GBM, may have potential as therapeutic targets. The prognostic value of VISTA expression was cross-validated in 180 glioma patients, and it was observed that patients with high VISTA expression had a poorer prognosis. In addition, multimodal cross analysis integrated SnRNA-seq and ST, revealing complex intracellular communication and mapping the GBM tumor microenvironment. This study reveals novel molecular characteristics of GBM, co-expression of immune checkpoints, and potential therapeutic targets, contributing to improving the understanding and treatment of GBM.

Keywords: Cell-cell communication; Glioblastoma; Immune checkpoints; Single-nucleus RNA sequencing; Spatial transcriptomics.