Abstract
Immune-checkpoint therapy has failed to show significant benefit in glioblastoma (GBM) patients. Immunologic subtypes of GBM are necessary to identify patients who might benefit from immune-checkpoint therapy. This study reviewed 152 GBM samples from The Cancer Genome Atlas (TCGA) and 214 GBM samples from Chinese Glioma Genome Atlas (CGGA). Correlation analysis showed that immune checkpoint genes (ICGs) were mainly positively correlated. The prognostic analysis of the overall survival showed that there was a significant correlation between the overall survival (OS) and the prognosis of ICGs, in which the TNFSF14 gene was a significant adverse prognostic factor. Combined with TMB and neoantigens, we found that TNFSF9 and CD27 were significantly negatively correlated with TMB and neoantigens. The association between adaptive immune pathway genes and ICG expression showed that they were positively correlated with ICGs, indicating that adaptive immune pathway genes have a certain regulatory effect on the expression of ICGs. The analysis of clinical features of the samples showed that the higher the expression of ICGs, the more likely to be correlated with mutant isocitrate dehydrogenase (IDH), while the lower the expression level of IDH, the more likely to be significantly correlated with the primary GBM. Survival analysis showed that low expression of PD-L1, IDO1, or CTLA4 with TNFSF14 in the low expression group had the best prognosis, while high expression of IDO1 or CD274 with TNFSF14 in the high expression group and low expression of CTLA4 with TNFSF14 in the high expression group had the worst prognosis. We conclude that TNFSF14 is a biomarker to identify immunologic subtype and prognosis with other ICGs in GBM and may serve as a potential therapeutic target.
Highlights
Gliomas are derived from glial cells and are the most prevalent type of primary tumor in the human brain
These 45 immune checkpoint genes (ICG) could be divided into three expression groups: high expression group, moderate expression group, and low expression group
The high expression group was represented by CD44 and CD276, and the expression level was generally high in all samples, while the moderate expression group was represented by CD48 and CD274 (PD-L1)
Summary
Gliomas are derived from glial cells and are the most prevalent type of primary tumor in the human brain. The incidence of GBM is 0.59–3.69/100,000 worldwide, and the median age of onset is 63.0 years. Standard therapies according to National Comprehensive Cancer Network (NCCN) guidelines include tumor resection, radiotherapy with concomitant temozolomide (TMZ), and adjuvant TMZ chemotherapy, with the combination of radiotherapy and other therapies. GBM patients have a very poor prognosis after routine surgery, radiotherapy, and chemotherapy. The five-year overall survival (OS) rate was 9.8%, while that of radiotherapy alone was 1.9%. The median survival time was only 12–15 months after diagnosis [1, 2]. Immunotherapy, including immune checkpoint blocking, chimeric antigen receptor T-cell therapy (CAR-T) and dendritic cell (DC) therapy, have introduced hope for glioma patients [7]
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