AUTHOR=Ait Ssi Saadia , Chraa Dounia , El Azhary Khadija , Sahraoui Souha , Olive Daniel , Badou Abdallah 

TITLE=Prognostic Gene Expression Signature in Patients With Distinct Glioma Grades

JOURNAL=Frontiers in Immunology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.685213

DOI=10.3389/fimmu.2021.685213

ISSN=1664-3224

ABSTRACT=Background: Glioma is the most common type of primary brain tumor in adults. Patients with the most malignant form have an overall survival time of < 16 months. Although considerable progress has been made in defining the adapted therapeutic strategies, measures to counteract tumor escape have not kept pace, due to the developed resistance of malignant glioma. In fact, identifying the nature and role of distinct tumor-infiltrating immune cells in glioma patients would decipher potential mechanisms behind therapy failure. 
 Methods: We integrated into our study, glioma transcriptomic datasets from the Cancer Genome Atlas (TCGA) cohort (154 GBM and 516 LGG patients). LM22 immune signature was built using Cibersort. hierarchical clustering and UMAP dimensional reduction algorithms were applied to identify clusters among glioma patients either in an unsupervised or supervised way. Furthermore, differential gene expression (DGE) has been performed to unravel the top expressed genes among the identified clusters. Besides, we used the least absolute shrinkage and selection operator (LASSO), Cox regression algorithm to set up the most valuable prognostic factor.
Results: Our study revealed, following gene enrichment analysis, the presence of two distinct groups of patients. The first group, defined as cluster 1, was characterized by the presence of immune cells known to exert efficient anti-tumoral immune response and was associated with better patients’ survival. Whereas, the second group cluster 2, which exhibited a poor survival, was enriched with cells and molecules, known to set an immunosuppressive pro-tumoral microenvironment. Interestingly, we revealed that gene expression signatures were also consistent with each immune cluster function. A strong presence of activated NK cells was revealed in cluster 1. In contrast, potent immunosuppressive components such as regulatory T cells, neutrophils, and M0/M1/M2macrophages were detected in cluster 2; where, in addition, inhibitory immune checkpoints, such as PD-1, CTLA-4 and TIM-3, were also significantly up-regulated. Finally, Cox regression analysis further corroborated that tumor infiltrating cells from cluster 2 exerted significant impact on patients’ prognosis.
Conclusion: Our work brings to light the tight implication of immune components on glioma patient’s prognosis. This would contribute to potentially develop better immune-based therapeutic approaches.