CD96, a new immune checkpoint, correlates with immune profile and clinical outcome of glioma

Abstract CD96 is a promising candidate for immunotherapy. However, its role and importance in glioma remains unknown. We thus aimed to genetically and clinically characterize CD96 expression in gliomas. For this, we extracted RNA-seq data of 699 glioma samples from the TCGA dataset and validated the...

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Autores principales: Fangkun Liu, Jing Huang, Fengqiong He, Xiaodong Ma, Fan Fan, Ming Meng, Yang Zhuo, Liyang Zhang
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Publicado: Nature Portfolio 2020
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spelling oai:doaj.org-article:cc2f23111ef7425386ea78d03e4895fc2021-12-02T18:18:50ZCD96, a new immune checkpoint, correlates with immune profile and clinical outcome of glioma10.1038/s41598-020-66806-z2045-2322https://doaj.org/article/cc2f23111ef7425386ea78d03e4895fc2020-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-66806-zhttps://doaj.org/toc/2045-2322Abstract CD96 is a promising candidate for immunotherapy. However, its role and importance in glioma remains unknown. We thus aimed to genetically and clinically characterize CD96 expression in gliomas. For this, we extracted RNA-seq data of 699 glioma samples from the TCGA dataset and validated these findings using the CGGA dataset comprising 325 glioma samples. Clinical and isocitrate dehydrogenase (IDH) mutation status were also analyzed. Various packages in R language were mainly used for statistical analysis. CD96 expression was significantly up-regulated in high-grade, IDH-wildtype, and mesenchymal-molecular subtype gliomas based on TCGA data, which was validated using the CGGA dataset. Subsequent gene ontology analysis of both datasets suggested that genes relevant to CD96 are mainly involved in immune functions in glioma as such genes were positively correlated with CD96 expression. To further explore the relationship between CD96 and immune responses, we selected seven immune-related metagenes and found that CD96 expression was positively correlated with HCK, LCK, and MHC II in the CGGA and TCGA cohorts but negatively associated with IgG. Further, Pearson correlation analysis showed that CD96 is associated with TIGIT, CD226, CRTAM, TIM-3, PD-L1, CTLA-4, and STAT3, indicating the additive antitumoral effects of these checkpoint proteins. CD96 was also suggested to play an important role in immune responses and positively collaborate with other checkpoint members. These findings show that CD96 is promising candidate for immunotherapy, and that such agents could complement current immunotherapy strategies for glioma.Fangkun LiuJing HuangFengqiong HeXiaodong MaFan FanMing MengYang ZhuoLiyang ZhangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-10 (2020)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Fangkun Liu
Jing Huang
Fengqiong He
Xiaodong Ma
Fan Fan
Ming Meng
Yang Zhuo
Liyang Zhang
CD96, a new immune checkpoint, correlates with immune profile and clinical outcome of glioma
description Abstract CD96 is a promising candidate for immunotherapy. However, its role and importance in glioma remains unknown. We thus aimed to genetically and clinically characterize CD96 expression in gliomas. For this, we extracted RNA-seq data of 699 glioma samples from the TCGA dataset and validated these findings using the CGGA dataset comprising 325 glioma samples. Clinical and isocitrate dehydrogenase (IDH) mutation status were also analyzed. Various packages in R language were mainly used for statistical analysis. CD96 expression was significantly up-regulated in high-grade, IDH-wildtype, and mesenchymal-molecular subtype gliomas based on TCGA data, which was validated using the CGGA dataset. Subsequent gene ontology analysis of both datasets suggested that genes relevant to CD96 are mainly involved in immune functions in glioma as such genes were positively correlated with CD96 expression. To further explore the relationship between CD96 and immune responses, we selected seven immune-related metagenes and found that CD96 expression was positively correlated with HCK, LCK, and MHC II in the CGGA and TCGA cohorts but negatively associated with IgG. Further, Pearson correlation analysis showed that CD96 is associated with TIGIT, CD226, CRTAM, TIM-3, PD-L1, CTLA-4, and STAT3, indicating the additive antitumoral effects of these checkpoint proteins. CD96 was also suggested to play an important role in immune responses and positively collaborate with other checkpoint members. These findings show that CD96 is promising candidate for immunotherapy, and that such agents could complement current immunotherapy strategies for glioma.
format article
author Fangkun Liu
Jing Huang
Fengqiong He
Xiaodong Ma
Fan Fan
Ming Meng
Yang Zhuo
Liyang Zhang
author_facet Fangkun Liu
Jing Huang
Fengqiong He
Xiaodong Ma
Fan Fan
Ming Meng
Yang Zhuo
Liyang Zhang
author_sort Fangkun Liu
title CD96, a new immune checkpoint, correlates with immune profile and clinical outcome of glioma
title_short CD96, a new immune checkpoint, correlates with immune profile and clinical outcome of glioma
title_full CD96, a new immune checkpoint, correlates with immune profile and clinical outcome of glioma
title_fullStr CD96, a new immune checkpoint, correlates with immune profile and clinical outcome of glioma
title_full_unstemmed CD96, a new immune checkpoint, correlates with immune profile and clinical outcome of glioma
title_sort cd96, a new immune checkpoint, correlates with immune profile and clinical outcome of glioma
publisher Nature Portfolio
publishDate 2020
url https://doaj.org/article/cc2f23111ef7425386ea78d03e4895fc
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