Clinical implication of cellular vaccine in glioma: current advances and future prospects

Yan, Yuanliang; Zeng, Shuangshuang; Gong, Zhicheng; Xu, Zhijie

doi:10.1186/s13046-020-01778-6

Cited by 36 publications

(31 citation statements)

References 145 publications

(144 reference statements)

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“…Over the past few years, several immunotherapeutic approaches have been developed (13); however, clinical trials testing vaccines, cell adoptive transfer, and immune checkpoint inhibitors (ICIs) point to a lack of efficacy (14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

Prognostic Gene Expression Signature in Patients With Distinct Glioma Grades

et al. 2021

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BackgroundGlioma is the most common type of primary brain tumor in adults. Patients with the most malignant form have an overall survival time of <16 months. Although considerable progress has been made in defining the adapted therapeutic strategies, measures to counteract tumor escape have not kept pace, due to the developed resistance of malignant glioma. In fact, identifying the nature and role of distinct tumor-infiltrating immune cells in glioma patients would decipher potential mechanisms behind therapy failure.MethodsWe integrated into our study glioma transcriptomic datasets from the Cancer Genome Atlas (TCGA) cohort (154 GBM and 516 LGG patients). LM22 immune signature was built using CIBERSORT. Hierarchical clustering and UMAP dimensional reduction algorithms were applied to identify clusters among glioma patients either in an unsupervised or supervised way. Furthermore, differential gene expression (DGE) has been performed to unravel the top expressed genes among the identified clusters. Besides, we used the least absolute shrinkage and selection operator (LASSO) and Cox regression algorithm to set up the most valuable prognostic factor.ResultsOur study revealed, following gene enrichment analysis, the presence of two distinct groups of patients. The first group, defined as cluster 1, was characterized by the presence of immune cells known to exert efficient antitumoral immune response and was associated with better patient survival, whereas the second group, cluster 2, which exhibited a poor survival, was enriched with cells and molecules, known to set an immunosuppressive pro-tumoral microenvironment. Interestingly, we revealed that gene expression signatures were also consistent with each immune cluster function. A strong presence of activated NK cells was revealed in cluster 1. In contrast, potent immunosuppressive components such as regulatory T cells, neutrophils, and M0/M1/M2 macrophages were detected in cluster 2, where, in addition, inhibitory immune checkpoints, such as PD-1, CTLA-4, and TIM-3, were also significantly upregulated. Finally, Cox regression analysis further corroborated that tumor-infiltrating cells from cluster 2 exerted a significant impact on patient prognosis.ConclusionOur work brings to light the tight implication of immune components on glioma patient prognosis. This would contribute to potentially developing better immune-based therapeutic approaches.

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Section: Introductionmentioning

confidence: 99%

Prognostic Gene Expression Signature in Patients With Distinct Glioma Grades

et al. 2021

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“…Several other multiple-epitope vaccines are also under development for glioma treatment [ 86 ]. Among these vaccines, the dendritic cell vaccine (DCVax-Brain) consists of purified dendritic cells and tumor antigens (#NCT00045968) [ 87 , 88 ], whereas the personalized cellular vaccine (PerCellVac2) is made up of allogeneic peripheral blood cells combined with autologous glioma antigens (#NCT02808364, #NCT02709616) [ 89 ].…”

Section: Resultsmentioning

confidence: 99%

Against the Resilience of High-Grade Gliomas: The Immunotherapeutic Approach (Part I)

Lucifero

Luzzi

2021

Brain Sciences

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The resilience of high-grade gliomas (HGGs) against conventional chemotherapies is due to their heterogeneous genetic landscape, adaptive phenotypic changes, and immune escape mechanisms. Innovative immunotherapies have been developed to counteract the immunosuppressive capability of gliomas. Nevertheless, further research is needed to assess the efficacy of the immuno-based approach. The aim of this study is to review the newest immunotherapeutic approaches for glioma, focusing on the drug types, mechanisms of action, clinical pieces of evidence, and future challenges. A PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis)-based literature search was performed on PubMed/Medline and ClinicalTrials.gov databases using the keywords “active/adoptive immunotherapy,” “monoclonal antibodies,” “vaccine,” and “engineered T cell.”, combined with “malignant brain tumor”, “high-grade glioma.” Only articles written in English published in the last 10 years were selected, filtered based on best relevance. Active immunotherapies include systemic temozolomide, monoclonal antibodies, and vaccines. In several preclinical and clinical trials, adoptive immunotherapies, including T, natural killer, and natural killer T engineered cells, have been shown to be potential treatment options for relapsing gliomas. Systemic temozolomide is considered the backbone for newly diagnosed HGGs. Bevacizumab and rindopepimut are promising second-line treatments. Adoptive immunotherapies have been proven for relapsing tumors, but further evidence is needed.

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“…Then, previous studies showed that immune cell infiltration plays a crucial role in tumorigenesis, prognosis and therapies ( Mukherjee et al, 2020 ; Xu et al, 2020c ; Yan et al, 2020 ). Most T cells and macrophage-mediated phagocytosis are capable of killing tumor cells and preventing tumor growth ( Feng et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

The bioinformatics and experimental analysis of AlkB family for prognosis and immune cell infiltration in hepatocellular carcinoma

Peng

Yan

2021

PeerJ

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Background Serving as N6-methyladenosine demethylases, the AlkB family is involved in the tumorigenesis of hepatocellular carcinoma (HCC). However, the molecular profiles and clinical values of the AlkB family in HCC are not well known. Methods Several bioinformatics tools and in vitro experiments were used to identify the immune-related profiles and prognostic values of AlkB family in HCC. Results In this study expression levels of ALKBH1/2/3/4/7 were all remarkably increased in HCC tissues when compared with normal tissues. Quantitative PCR (qPCR) and immunohistochemistry were used to validate the expression of AlkB family members in HCC tissues and normal liver tissues. In addition, high expression levels of ALKBH4 were negatively correlated with overall survival (OS) and disease-free survival (DFS) in patients with HCC. Increased ALKBH4 was also associated with pathological stage in HCC patients. The molecular profiles of AlkB family in HCC were mainly associated with peptidyl-serine modification, peptidyl-tyrosine modification, regulation of metal ion transport, etc. Furthermore, tumor-infiltrating immune cell analysis indicated that ALKBH1/2/3/4/5/6/7/8 and FTO were related to the infiltration of different immune cell, such as CD8+ T cells, macrophages, neutrophils, dendritic cells and CD4+ T cells. We also discovered that the methylation levels of ALKBH1/2/4/5/6/8 and FTO were remarkably reduced in HCC tissues. Conclusions Collectively, our findings may deepen the understanding of specific molecular profiles of the AlkB family in HCC pathology. In particular, ALKBH4 could serve as a promising prognostic candidate for treating HCC, and these results might potentiate the development of more reliable therapeutic strategies for patients with HCC.

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Clinical implication of cellular vaccine in glioma: current advances and future prospects

Cited by 36 publications

References 145 publications

Prognostic Gene Expression Signature in Patients With Distinct Glioma Grades

Prognostic Gene Expression Signature in Patients With Distinct Glioma Grades

Against the Resilience of High-Grade Gliomas: The Immunotherapeutic Approach (Part I)

The bioinformatics and experimental analysis of AlkB family for prognosis and immune cell infiltration in hepatocellular carcinoma

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