Oxidative stress is involved in immunosuppression and macrophage regulation in glioblastoma

Xisong Liang; Zeyu Wang; Ziyu Dai; Jian Liu; Hao Zhang; Jie Wen; Nan Zhang; Jian Zhang; Peng Luo; Zaoqu Liu; Zhixiong Liu; Quan Cheng

doi:10.1016/j.clim.2023.109802

Oxidative stress is involved in immunosuppression and macrophage regulation in glioblastoma

Clin Immunol. 2024 Jan:258:109802. doi: 10.1016/j.clim.2023.109802. Epub 2023 Oct 20.

Authors

Xisong Liang¹, Zeyu Wang¹, Ziyu Dai¹, Jian Liu², Hao Zhang¹, Jie Wen¹, Nan Zhang³, Jian Zhang⁴, Peng Luo⁴, Zaoqu Liu⁵, Zhixiong Liu⁶, Quan Cheng⁷

Affiliations

¹ Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, PR China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, PR China.
² Experiment Center of Medical Innovation, The First Hospital of Hunan University of Chinese Medicine, Changsha, 410007, Hunan, China.
³ College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, Hubei, PR China.
⁴ Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou 510000, Guangdong, PR China.
⁵ Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, PR China.
⁶ Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, PR China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, PR China. Electronic address: zhixiongliu@csu.edu.cn.
⁷ Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, PR China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, PR China; Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, PR China. Electronic address: chengquan@csu.edu.cn.

PMID: 37866784
DOI: 10.1016/j.clim.2023.109802

Abstract

Oxidative stress dually affected cancer progression, while its effect on glioblastomas remained unclear. Herein, we clustered the multicenter glioblastoma cohorts based on the oxidative-stress-responsive genes (OSS) expression. We found that cluster 2 with high OSS levels suffered a worse prognosis. Functional analyses and immune-related analyses results exhibited that M2-like pro-tumoral macrophages and neutrophils were enriched in cluster 2, while Natural killer cells' infiltration was decreased. The increased M2-like pro-tumoral macrophages in cluster 2 was confirmed by immunofluorescence. An integrated single-cell analysis validated the malignant features of cluster 2 neoplastic cells and discovered their crosstalk with M2-like pro-tumoral macrophages. Moreover, we observed that SOD3 knockdown might decrease the M2-like pro-tumoral transformation of macrophage in vitro and in vivo. Comprehensively, we revealed oxidative stress' prognostic and immunosuppressive potential in glioblastoma and discovered SOD3's potential role in regulating macrophage M2-like pro-tumoral transformation.

Keywords: Glioblastoma; Macrophage; Microglia; Oxidative stress; SOD3.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Brain Neoplasms* / genetics
Brain Neoplasms* / pathology
Glioblastoma* / genetics
Glioblastoma* / pathology
Humans
Immunosuppression Therapy
Macrophages
Oxidative Stress
Tumor Microenvironment