Single-cell RNA sequencing for characterizing the immune communication and iron metabolism roles in CD31+ glioma cells

Yiming Guan; Yu Luan; Shanshan Zhao; Meiyan Li; Francesco Girolamo; Joshua D Palmer; Qi Guan

doi:10.21037/tcr-2025-377

Single-cell RNA sequencing for characterizing the immune communication and iron metabolism roles in CD31⁺ glioma cells

Transl Cancer Res. 2025 Apr 30;14(4):2421-2439. doi: 10.21037/tcr-2025-377. Epub 2025 Apr 25.

Authors

Yiming Guan¹, Yu Luan², Shanshan Zhao², Meiyan Li³, Francesco Girolamo⁴, Joshua D Palmer⁵, Qi Guan²

Affiliations

¹ Department of Surgery and Cancer, Imperial College London, London, UK.
² Clinical Laboratory Center, The First People's Hospital of Shenyang (Shenyang Brain Hospital), Shenyang Medical College, Shenyang, China.
³ Tuberculosis Laboratory, Shenyang Tenth People's Hospital (Shenyang Chest Hospital), Shenyang, China.
⁴ Department of Translational Biomedicine and Neuroscience (DiBraiN), University of Bari Aldo Moro, Bari, Italy.
⁵ Department of Radiation Oncology, Ohio State University, Columbus, OH, USA.

Abstract

Background: Gliomas are aggressive brain tumors marked by complex cellular interactions and significant immune cell infiltration. This study investigated the role of CD31⁺ immune cells, specifically macrophages and T cells, in the glioma microenvironment through single-cell RNA sequencing (scRNA-seq).

Methods: We employed the CellChat framework to map cell-cell communication pathways and used Monocle3 for pseudotime trajectory analysis to characterize the signaling and developmental progressions within CD31⁺ cells. Pathways such as osteopontin (SPP1) and major histocompatibility complex class II (MHC-II) were analyzed in terms of their role in immune regulation, and we examined the expression of ferritin, an iron-binding protein, to assess its potential function in modulating CD31⁺ cell activity.

Results: Our findings highlight the expression of key pathways, including SPP1 and MHC-II, influencing immune regulation. Ferritin was found to be highly expressed in CD31⁺ cells, suggesting a dual role in iron metabolism and immune modulation within the glioma microenvironment.

Conclusions: This study clarified the distinct roles of CD31⁺ immune cells in glioma progression and identified ferritin as a potential therapeutic target for modulating immune responses in gliomas. These findings may offer new directions in glioma research and the development of immunotherapy, which can aid in improving treatment outcomes.

Keywords: CD31; ferritin; glioma; immune regulation; tumor microenvironment.