Immunotherapy for glioma: Current management and future application

Xu, Shengchao; Tang, Lu; Li, Xizhe; Fan, Fan; Zhi-xiong, Liu

doi:10.1016/j.canlet.2020.02.002

Cited by 376 publications

(276 citation statements)

References 153 publications

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“…These immune cells include lymphocytes, natural killer (NK) cells, dendritic cells, macrophages, neutrophils, and so on (9). With the deep understanding of the tumor microenvironment, immunotherapy recently has been developed to be a more effective treatment for aggressive cancers (10)(11)(12)(13). For example, multiple therapeutic antibodies that block immune checkpoints, such as cytotoxic T lymphocyte associated antigen 4 (CTLA4) and programmed cell death protein 1 (PD1), showed great effects in treating non-small-cell lung cancer, kidney cancer, and melanoma (14).…”

Section: Introductionmentioning

confidence: 99%

Development and Validation of a Tumor Mutation Burden–Related Immune Prognostic Model for Lower-Grade Glioma

Jiang

Tan

et al. 2020

Front. Oncol.

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Tumor mutation burden (TMB) is a useful biomarker to predict prognosis and the efficacy of immune checkpoint inhibitors (ICIs). In this study, we aimed to explore the prognostic value of TMB and the potential association between TMB and immune infiltration in lower-grade gliomas (LGGs). Somatic mutation and RNA-sequencing (RNA-seq) data were downloaded from the Cancer Genome Atlas (TCGA) database. TMB was calculated and patients were divided into high- and low-TMB groups. After performing differential analysis between high- and low-risk groups, we identified six hub TMB and immune-related genes that were correlated with overall survival in LGGs. Then, Gene Set Enrichment Analysis was performed to screen significantly enriched GO terms between the two groups. Moreover, an immune-related risk score system was developed by LASSO Cox analysis based on the six hub genes and was validated with the Chinese Glioma Genome Atlas dataset. Using the TIMER database, we further systematically analyzed the relationships between mutants of the six hub genes and immune infiltration levels, as well as the relationships between the immune-related risk score system and the immune microenvironment in LGGs. The results showed that TMB was negatively correlated with OS and high TMB might inhibit immune infiltration in LGGs. Furthermore, the risk score system could effectively stratify patients into low- and high-risk groups in both the training and validation datasets. Multivariate Cox analysis demonstrated that TMB was not an independent prognostic factor, but the risk score was. Higher infiltration of immune cells (B cells, CD4 + T cells, CD8 + T cells, neutrophils, macrophages, and dendritic cells) and higher levels of immune checkpoints (PD-1, CTLA-4, LAG-3, and TIM-3) were found in patients in the high-risk group. Finally, a novel nomogram model was constructed and evaluated to estimate the overall survival of LGG patients. In summary, our study provided new insights into immune infiltration in the tumor microenvironment and immunotherapies for LGGs.

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Section: Introductionmentioning

confidence: 99%

Development and Validation of a Tumor Mutation Burden–Related Immune Prognostic Model for Lower-Grade Glioma

Jiang

Tan

et al. 2020

Front. Oncol.

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“…High mutational load with increased neo-antigens correlates strongly with immunotherapy efficacy in patients [ 37 ], while those with low mutational loads, such as GBM, exhibit little response [ 38 ]. However, GBM has better responses to oncolytic viral therapy, although many patients also respond to standard care [ 3 ]. Previous studies demonstrated that engineered OAd elicited good response in GBM [ 8 , 39 ].…”

Section: Discussionmentioning

confidence: 99%

“…Glioblastoma (GBM) remains a refractory and lethal disease despite decades of comprehensive research. GBM expresses a variety of proteins that bind to T cell surface receptors, leading to T cell dysfunction and apoptosis [ 1 , 2 ], and GBM microenvironment signals, such as TGF-β and IL-10, induce local and systemic immunosuppression [ 3 ]. Despite the introduction of concomitant and adjuvant radiotherapy and chemotherapy, patient prognosis remains unsatisfactory, with an almost 15 months median survival [ 4 – 6 ].…”

Section: Introductionmentioning

confidence: 99%

Efficacy of a novel double-controlled oncolytic adenovirus driven by the Ki67 core promoter and armed with IL-15 against glioblastoma cells

Zhang

Tian

et al. 2020

Cell Biosci

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Background Glioblastoma (GBM) is an immunosuppressive, highly vascular and devastating malignant brain tumor. Even with progressive combination treatment that includes surgery, radiotherapy, and chemotherapy, the prognosis for GBM patients is still extremely poor. Oncolytic adenovirus (OAd) can specifically replicate in GBM cells, permitting the rapid copy of the therapeutic genes it carries. Moreover, E1A is an essential gene in adenoviral replication and is the first gene expressed upon viral infection. E1A expression can be regulated by the Ki67 promoter, while the CMV promoter drives therapeutic gene expression. However, the efficacy of a double-controlled OAd driven by the Ki67 core promoter and armed with IL-15 against GBM cells has not been investigated. Methods Fluorescence microscopy was performed to evaluate infection ability in the viruses. Cell viability was detected by CCK-8 assay. Levels of cytokines in different supernatants were determined by ELISA, and IL-15 gene expression was measured by RT-PCR. Angiogenic capacity was analyzed by tube formation assay. Results We successfully constructed a double-controlled oncolytic adenovirus driven by the Ki67 core promoter and armed with IL-15 that selectively infected and killed GBM cells while sparing normal cells. The adenoviruses prime IL-15 gene expression to significantly enhance anti-GBM efficacy through effective activation of microglial cells. Moreover, OAd not only directly inhibits angiogenesis but exhibits potent antiangiogenic capacity mediated by the reduction of VEGF secretion. Conclusions These results provide new insight into the effects of a novel double-controlled OAd driven by the Ki67 core promoter and armed with IL-15 in glioblastoma treatment, which may help in the development of novel therapies in solid tumors.

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“…Glioma is a deadly tumor in the central nervous system [ 1 ], while glioblastoma (GBM) is the most malignant type of gliomas [ 2 ]. Surgical resection, adjuvant chemotherapy, postoperative radiotherapy, and immunotherapy form the standard treatment for gliomas [ 3 – 5 ]. Despite advances in techniques and equipment in surgery for gliomas, the overall survival (OS) rate of patients with glioma is still poor [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

The Prognostic Role of Glutathione Peroxidase 1 and Immune Infiltrates in Glioma Investigated Using Public Datasets

Luo

Huang

et al. 2020

Med Sci Monit

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Immunotherapy for glioma: Current management and future application

Cited by 376 publications

References 153 publications

Development and Validation of a Tumor Mutation Burden–Related Immune Prognostic Model for Lower-Grade Glioma

Development and Validation of a Tumor Mutation Burden–Related Immune Prognostic Model for Lower-Grade Glioma

Efficacy of a novel double-controlled oncolytic adenovirus driven by the Ki67 core promoter and armed with IL-15 against glioblastoma cells

The Prognostic Role of Glutathione Peroxidase 1 and Immune Infiltrates in Glioma Investigated Using Public Datasets

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