Identification of Promising Antagonists of the Tumor Microenvironment Immunosuppressive Adenosine 2A Receptor through a Pharmacoinformatics- Based Approach

Rafii, Soumaya; Ghallab, Yassine El; Ghouzlani, Amina; Kandoussi, Sarah; Badou, Abdallah

doi:10.26502/jbsb.5107025

Cited by 2 publications

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“…Furthermore, the A 2A R has a strong affinity for adenosine [ 13 ]. We directed our research towards the study of the A 2A R in gliomas, it is an inhibitory checkpoint of the immune system, which by blocking it with an antagonist has shown efficacy in other types of cancer, by improving the anti-tumor immune response [ 14 , 15 , 16 , 17 , 18 ]. This receptor is highly expressed in lymphocytes, macrophages, mast cells, neutrophils, dendritic cells, eosinophils, NK cells, endothelial cells, and epithelial cells [ 19 ].…”

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confidence: 99%

A2AR as a Prognostic Marker and a Potential Immunotherapy Target in Human Glioma

Rafii

Ghouzlani

Naji

et al. 2023

IJMS

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Gliomas are considered one of the most malignant tumors in the body. The immune system has the ability to control the initiation and development of tumors, including gliomas. Thus, immune cells find themselves controlled by various molecular pathways, inhibiting their activation, such as the immunosuppressive adenosine 2A receptor (A2AR). Our objective was to establish the expression profile and role of A2AR at the transcriptomic level, using real-time RT-PCR in Moroccan glioma patients, in addition to TCGA and CGGA cohorts. The real-time RT-PCR results in Moroccan patients showed that high expression of this gene was associated with poor survival in males. Our study on the CGGA cohort corroborated these results. In addition, there was a positive association of A2AR with T-cell exhaustion genes. A2AR also correlated strongly with genes that are primarily enriched in focal adhesion and extracellular matrix interactions, inducing epithelial mesenchymal transition, angiogenesis, and glioma growth. However, in the TCGA cohort, the A2AR showed results that were different from the two previously examined cohorts. In fact, this gene was instead linked to a good prognosis in patients with the astrocytoma histological type. The correlation and enrichment results reinforced the prognostic role of A2AR in this TCGA cohort, in which its high expression was shown to be related to lymphocyte differentiation and a successful cytolytic response, suggesting a more efficient anti-tumor immune response. Correlations and differential analyses based on A2AR gene expression, to understand the cause of the association of this gene with two different prognoses (CGGA males and TCGA Astrocytoma), showed that the overexpression of A2AR in Chinese male patients could be associated with the overexpression of extracellular adenosine, which binds to A2AR to induce immunosuppression and consequently a poor prognosis. However, in the second group (TCGA astrocytomas), the overexpression of the gene could be associated with an adenosine deficiency, and therefore this receptor does not undergo activation. The absence of A2AR activation in these patients may have protected them from immunosuppression, which could reflect the good prognosis. A2AR can be considered a promising therapeutic target in male CGGA and Moroccan patients with gliomas.

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