The immune checkpoint VISTA exhibits high expression levels in human gliomas and associates with a poor prognosis

Abstract In human gliomas, anti-tumor T cell responses are inhibited through induction of local and systemic immunosuppression. Immune checkpoint blockade is proving to be a success in several types of cancers. However, many studies reported that the treatment of glioblastoma patients with anti-CTLA...

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Autores principales:	Amina Ghouzlani, Abdelhakim Lakhdar, Soumaya Rafii, Mehdi Karkouri, Abdallah Badou
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2d63a8a9061749b18bfd3005525a1a84
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spelling	oai:doaj.org-article:2d63a8a9061749b18bfd3005525a1a842021-11-08T10:49:18ZThe immune checkpoint VISTA exhibits high expression levels in human gliomas and associates with a poor prognosis10.1038/s41598-021-00835-02045-2322https://doaj.org/article/2d63a8a9061749b18bfd3005525a1a842021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-00835-0https://doaj.org/toc/2045-2322Abstract In human gliomas, anti-tumor T cell responses are inhibited through induction of local and systemic immunosuppression. Immune checkpoint blockade is proving to be a success in several types of cancers. However, many studies reported that the treatment of glioblastoma patients with anti-CTLA-4 or anti-PD-1 has no survival benefit compared to standard chemotherapy. This study aimed to investigate the expression and role of VISTA, a newly described immune checkpoint regulator, in human gliomas. mRNA expression was assessed in a total of 87 samples from glioma patients. 57 glioma tissues were taken at different grades. 20 peripheral blood mononuclear cells (PBMC) samples were taken before surgery and ten after surgery, all from the same set of patients. As for the control, ten specimens of PBMC were taken from healthy donors. Protein expression using immunohistochemistry was performed for 30 patients. The Cancer Genome Atlas (TCGA) data set, was also used to investigate VISTA expression through analysis of RNA-seq data of 667 glioma patients. In the Moroccan cohort, VISTA gene expression was significantly upregulated in glioma tissues related to PBMC of healthy donors. This high expression was specific to patient tissues since VISTA expression in PBMC was low when assessed either before or after surgery. Besides, VISTA exhibited higher expression levels in grade III/IV relative to grade I/II glioma patients. Interestingly, VISTA correlated positively with PD-1 expression. PD-1 also showed elevated expressions in higher glioma grades. The TCGA cohort corroborated these observations. Indeed, VISTA was also found to be strongly expressed in high grades. It was positively correlated with other critical immune checkpoints. Finally, increased VISTA transcript levels were associated with weak overall survival of glioma patients. Our study highlighted a correlation between high levels of VISTA expression and poor prognosis in glioma patients. VISTA might be involved in glioma progression and could be considered as a possible new therapeutic target, especially in advanced gliomas.Amina GhouzlaniAbdelhakim LakhdarSoumaya RafiiMehdi KarkouriAbdallah BadouNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Amina Ghouzlani Abdelhakim Lakhdar Soumaya Rafii Mehdi Karkouri Abdallah Badou The immune checkpoint VISTA exhibits high expression levels in human gliomas and associates with a poor prognosis
description	Abstract In human gliomas, anti-tumor T cell responses are inhibited through induction of local and systemic immunosuppression. Immune checkpoint blockade is proving to be a success in several types of cancers. However, many studies reported that the treatment of glioblastoma patients with anti-CTLA-4 or anti-PD-1 has no survival benefit compared to standard chemotherapy. This study aimed to investigate the expression and role of VISTA, a newly described immune checkpoint regulator, in human gliomas. mRNA expression was assessed in a total of 87 samples from glioma patients. 57 glioma tissues were taken at different grades. 20 peripheral blood mononuclear cells (PBMC) samples were taken before surgery and ten after surgery, all from the same set of patients. As for the control, ten specimens of PBMC were taken from healthy donors. Protein expression using immunohistochemistry was performed for 30 patients. The Cancer Genome Atlas (TCGA) data set, was also used to investigate VISTA expression through analysis of RNA-seq data of 667 glioma patients. In the Moroccan cohort, VISTA gene expression was significantly upregulated in glioma tissues related to PBMC of healthy donors. This high expression was specific to patient tissues since VISTA expression in PBMC was low when assessed either before or after surgery. Besides, VISTA exhibited higher expression levels in grade III/IV relative to grade I/II glioma patients. Interestingly, VISTA correlated positively with PD-1 expression. PD-1 also showed elevated expressions in higher glioma grades. The TCGA cohort corroborated these observations. Indeed, VISTA was also found to be strongly expressed in high grades. It was positively correlated with other critical immune checkpoints. Finally, increased VISTA transcript levels were associated with weak overall survival of glioma patients. Our study highlighted a correlation between high levels of VISTA expression and poor prognosis in glioma patients. VISTA might be involved in glioma progression and could be considered as a possible new therapeutic target, especially in advanced gliomas.
format	article
author	Amina Ghouzlani Abdelhakim Lakhdar Soumaya Rafii Mehdi Karkouri Abdallah Badou
author_facet	Amina Ghouzlani Abdelhakim Lakhdar Soumaya Rafii Mehdi Karkouri Abdallah Badou
author_sort	Amina Ghouzlani
title	The immune checkpoint VISTA exhibits high expression levels in human gliomas and associates with a poor prognosis
title_short	The immune checkpoint VISTA exhibits high expression levels in human gliomas and associates with a poor prognosis
title_full	The immune checkpoint VISTA exhibits high expression levels in human gliomas and associates with a poor prognosis
title_fullStr	The immune checkpoint VISTA exhibits high expression levels in human gliomas and associates with a poor prognosis
title_full_unstemmed	The immune checkpoint VISTA exhibits high expression levels in human gliomas and associates with a poor prognosis
title_sort	immune checkpoint vista exhibits high expression levels in human gliomas and associates with a poor prognosis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2d63a8a9061749b18bfd3005525a1a84
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The immune checkpoint VISTA exhibits high expression levels in human gliomas and associates with a poor prognosis

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