TMIGD2 as a potential therapeutic target in glioma patients

Frontiers in Immunology

Immunology

Abdelhakim Lakhdar¹  Saadia AIT SSI²  Chaimae Boulhen²  Hamza Benthami²  Abdallah Badou³  Ibtissam Razzouki⁴  Mehdi Karkouri⁴ 

[1] Department of Neurosurgery, Faculty of Medicine and Pharmacy, University of Hassan II, Casablanca, Morocco;Immuno-Genetics and Human Pathology Laboratory, Faculty of Medicine and Pharmacy, Hassan II University, Casablanca, Morocco;Immuno-Genetics and Human Pathology Laboratory, Faculty of Medicine and Pharmacy, Hassan II University, Casablanca, Morocco;Mohammed VI Center for Research and Innovation, Rabat, Morocco and Mohammed VI University of Sciences and Health, Casablanca, Morocco;Laboratory of Pathological Anatomy, University Hospital Center (CHU) Ibn Rochd, Hassan II University, Casablanca, Morocco;

关键词: TMIGD2;    glioma;    costimulatory;    immunotherapy;    prognosis;   

DOI  :  10.3389/fimmu.2023.1173518

 received in 2023-02-24, accepted in 2023-04-21,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionAmong all types of central nervous system cancers, glioma remains the most frequent primary brain tumor in adults. Despite significant advances in immunomodulatory therapies, notably immune checkpoint inhibitors, their effectiveness remains constrained due to glioma resistance. The discovery of TMIGD2 (Transmembrane and Immunoglobulin Domain Containing 2) as an immuno-stimulatory receptor, constitutively expressed on naive T cells and most natural killer (NK) cells, has emerged as an attractive immunotherapy target in a variety of cancers. The expression profile of TMIGD2 and its significance in the overall survival of glioma patients remains unknown.MethodsIn the present study, we first assessed TMIGD2 mRNA expression using the Cancer Genome Atlas (TCGA) glioma transcriptome dataset (667 patients), followed by validation with the Chinese Glioma Genome Atlas (CGGA) cohort (693 patients). Secondly, we examined TMIGD2 protein staining in a series of 25 paraffin-embedded blocks from Moroccan glioma patients. The statistical analysis was performed using GraphPad Prism 8 software.ResultsTMIGD2 expression was found to be significantly higher in astrocytoma, IDH-1 mutations, low-grade, and young glioma patients. TMIGD2 was expressed on immune cells and, surprisingly, on tumor cells of glioma patients. Interestingly, our study demonstrated that TMIGD2 expression was negatively correlated with angiogenesis, hypoxia, G2/M checkpoint, and epithelial to mesenchymal transition signaling pathways. We also demonstrated that dendritic cells, monocytes, NK cells, gd T cells, and naive CD8 T cell infiltration correlates positively with TMIGD2 expression. On the other hand, Mantel-Cox analysis demonstrated that increased expression of TMIGD2 in human gliomas is associated with good overall survival. Cox multivariable analysis revealed that TMIGD2 is an independent predictor of a good prognosis in glioma patients.DiscussionTaken together, our results highlight the tight implication of TMIGD2 in glioma progression and show its promising therapeutic potential as a stimulatory target for immunotherapy.

【 授权许可】

Unknown   
Copyright © 2023 Boulhen, AIT SSI, Benthami, Razzouki, Lakhdar, Karkouri and Badou