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TIGIT is Positively Associated with Advanced Human Glioma and Displays an Immunosuppressive Microenvironment

Article scientifique 2022 Anglais

Résumé

Abstract Background: Diffuse glioma is a malignant human brain cancer that is hard to overcome. This represents a high risk of mortality. The current challenge is limited to the control of tumor progression and survival improvement.Immunotherapy consists of stimulating the immune system in order to eliminate the non-self-elements that damage the human body, including cancer cells. However, in human glioma, the current immunotherapeutic targets did not show significant benefit. In this study, we aimed at evaluating the expression and potential role of a new immunosuppressive molecule, TIGIT in glioma patients. Patients and Methods: A cohort of 667 patients from the TCGA database along with a cohort of 53 Moroccan patients, were analyzed in order to assess the role of TIGIT in human glioma progression and to estimate whether blocking this immune checkpoint molecule would be of a potential therapeutic benefit.Real time RT-PCR from fresh human biopsies and bioinformatics approaches were both used in this study. Results: Our results showed that high expression of TIGIT had prognostic value with some known clinical glioma risk factors such as sex, age and mutation status. High expression of TIGIT was positively associated with an advanced grade of glioma. Moreover, elevated levels of TIGIT were correlated to higher rates of FoxP3, a regulatory T-cell marker that reflects a strong immunosuppressive microenvironment. Interestingly, TIGIT showed strong association with Treg cell-secreted cytokines (TGF-beta and IL-10), supporting the likely involvement of TIGIT in the exhaustion of the intra-tumoral immune cells. Finally, elevated rates of TIGIT were significantly associated to elevated rates of other inhibitory immune checkpoint molecules (PD-1, VISTA and Tim-3) in human glioma patients.Conclusions: TIGIT blockade might be of valuable therapeutic benefit in patients with advanced gliomas.

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Qandouci, A., Ghouzlani, A., Kone, A., Lakhdar, A., Badou, A. (2022). TIGIT is Positively Associated with Advanced Human Glioma and Displays an Immunosuppressive Microenvironment. https://doi.org/10.21203/rs.3.rs-1530119/v1

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Auteur(s)

Ahmed Qandouci Amina Ghouzlani Abdou-samad Kone Abdelhakim Lakhdar Abdallah Badou

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