Astrocytoma represents a malignant brain tumor. Therapeutic strategies, including immunotherapy, are in continuous development to ameliorate the overall survival. Several immune checkpoints like CD155 and TIGIT were explored for this purpose. Still, the specific mAb against these molecules showed very limited outcome, which supports the need of investigating other strategies to block this pathway such as small-molecules drugs. In this study, bioinformatics approaches were used to answer our question. First, TCGA database was explored to evaluate the implication of CD155 and TIGIT in the progression of malignant astrocytoma. Then CIBERSORT analysis was used to analyze the difference of immune infiltration depending on TIGIT expression. Finally, a novel drug discovery method, using structure-based docking to find effective small molecules that target CD155/TIGIT pathway was used. Our results report that CD155 and TIGIT are significantly associated with clinical data including age, IDH-status, grade and molecular subtype of glioblastoma. Also, our data indicate that high expression of both CD155 and TIGIT are associated to worse overall survival. Furthermore, the CIBERSORT analysis showed the association of this pathway with an inflammatory microenvironment. Finally, the virtual screening allowed the identification of asteoside and rutin, as inhibitor small-molecules to CD155/TIGIT pathway, suggesting their potential to stimulate the immune system against the progression of astrocytoma.
Qandouci, Ahmed; Azhary, Khadija El; Souat, Sanaa; and Badou, Abdallah
"Identification of two potential small-molecules that inhibit the CD155/TIGIT pathway in human astrocytoma,"
Health Sciences: Vol. 4
, Article 1.
Available at: https://doi.org/10.56264/2658-865X.1078
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.