Cytomegalovirus as an oncomodulatory agent in the progression of glioma

Joseph, Gabriel P.; McDermott, Ryan; Барышникова, М. А.; Cobbs, Charles S.; Ulasov, Ilya V.

doi:10.1016/j.canlet.2016.10.022

Cited by 49 publications

(30 citation statements)

References 96 publications

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“…Wu et al, 2015). Like others in this area of research (Joseph et al, 2017), we believe that the mechanisms surrounding the clinical targeting of HCMV in GBM patients need to be further explored. As shown by multiple trials, there are promising clinical targets but the mechanism of the therapeutic effect is likely not as straightforward as direct targeting of HCMV.…”

Section: Discussionmentioning

confidence: 81%

“…It is well established that HCMV is often detected in greater than 90% of sampled GBM patients (Joseph et al, 2017). The mechanisms causing the high rate of HCMV can even be explained by the deficient immune response in GBM and the ability of HCMV to infect glial cells (McFaline-Figueroa & Wen, 2017).…”

Section: Discussionmentioning

confidence: 99%

“…Most of this debate stems from the fact that different research groups, often using different assays, have generated evidence to support or refute the presence of HCMV in GBM tumors. There is a large amount of research supporting both sides of this issue (Amirian, Bondy, Mo, Bainbridge, & Scheurer, 2014; Baryawno et al, 2011; Baumgarten et al, 2014; Cosset et al, 2014; Fornara et al, 2016; Hashida et al, 2015; Holdhoff et al, 2015; Joseph, McDermott, Baryshnikova, Cobbs, & Ulasov, 2017; Khoury et al, 2013; Lehrer, Green, Rosenzweig, & Rendo, 2015; Libard et al, 2014; McFaline-Figueroa & Wen, 2017; Prins, Cloughesy, & Liau, 2008; Rahbar et al, 2012; Sardi et al, 2015; Schelhorn et al, 2013; Shamran et al, 2015; Solomon, Ramkissoon, Milner, & Folkerth, 2014; Stangherlin et al, 2016; Strong et al, 2016; Wolmer-Solberg et al, 2013) that we summarize in Fig. 1B–D.…”

Section: Introductionmentioning

confidence: 91%

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Lack of human cytomegalovirus expression in single cells from glioblastoma tumors and cell lines

Johnson

Abrams

et al. 2017

J. Neurovirol.

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The relationship between human cytomegalovirus (HCMV) and glioblastoma (GBM) is an ongoing debate with extensive evidence supporting or refuting its existence through molecular assays, pre-clinical studies, and clinical trials. We focus primarily on the crux of the debate, detection of HCMV in GBM samples using molecular assays. We propose that these differences in detection could be affected by cellular heterogeneity. To take this into account we align the single-cell RNA sequencing (scRNA-seq) reads from 5 GBM tumors and 2 cell lines to HCMV, and analyze the alignments for evidence of i) complete viral transcripts and ii) low-abundance viral reads. We found that neither tumor nor cell line samples showed conclusive evidence of full HCMV viral transcripts. We also identified low-abundance reads aligned across all tumors, with two tumors having higher alignment rates than the rest of the tumor samples. This work is meant to rigorously test for HCMV RNA expression at a single cell level in GBM samples and examine the possible utility of single cell data in tumor virology.

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Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 91%

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Lack of human cytomegalovirus expression in single cells from glioblastoma tumors and cell lines

Johnson

Abrams

et al. 2017

J. Neurovirol.

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“…Although several GBM-specific targets for immunotherapy have been identified, such as EGFRvIII and IL13Rα2, these a b molecules are, unfortunately, only targetable in a limited percentage (< 30%) of GBM patients [46]. Recently, there have been reports demonstrating the presence of cytomegalovirus (CMV) in more than 90% of GBM patients [47][48][49] examined and though some established relationship between CMV persistence [50][51][52] and glioma tumorigenesis has been elucidated, this intriguing correlation and its potential for targeted immunotherapy inspired us to further verify the presence of CMV immediate early gene product (CMV-IE) in patientderived glioma tissues (Fig. 5A).…”

Section: Confirmation Of Gbm-specific Tumor Antigen (Cmv-ie) Expressimentioning

confidence: 99%

A Dendritic Cell-Targeted Adenoviral Vector Facilitates Adaptive Immune Response Against Human Glioma Antigen (CMV-IE) and Prolongs Survival in a Human Glioma Tumor Model

Kim¹,

Kane²,

Panek³

et al. 2018

Neurotherapeutics

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Antitumor immunotherapeutic strategies represent an especially promising set of approaches with rapid translational potential considering the dismal clinical context of high-grade gliomas. Dendritic cells (DCs) are the body's most professional antigen-presenting cells, able to recruit and activate T cells to stimulate an adaptive immune response. In this regard, specific loading of tumor-specific antigen onto dendritic cells potentially represents one of the most advanced strategies to achieve effective antitumor immunization. In this study, we developed a DC-specific adenoviral (Ad) vector, named Ad5scFvDEC205FF, targeting the DC surface receptor, DEC205. In vitro analysis shows that 60% of DCs was infected by this vector while the infectivity of other control adenoviral vectors was less than 10%, demonstrating superior infectivity on DCs. Moreover, an average of 14% of DCs were infected by Ad5scFvDEC205FF-GFP, while less than 3% of non-DCs were infected following in vivo administration, demonstrating highly selective in vivo DC infection. Importantly, vaccination with this vehicle expressing human glioma-specific antigen, Ad5scFvDEC205FF-CMV-IE, shows a prolonged survival benefit in GL261-implanted murine glioma models (p < 0.0007). Furthermore, when rechallenged, cancerous cells were completely rejected. In conclusion, our novel, viral-mediated, DC-based immunization approach has the significant therapeutic potential for patients with high-grade gliomas.

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“…[31] The second hypothesis is that HCMV may be oncomodulatory, thereby enhancing tumor progression by a specific mechanism or a combination of mechanisms, which were detailed in the previous section. [17,18,20,[22][23][24][26][27][28][29]32,33] The third hypothesis is that HCMV may be a bystander with little effect on tumor growth, and the HCMV antigens are expressed because of the highly immunosuppressive tumor microenvironment observed in GBM. There is no direct evidence to date to support this concept.…”

Section: Hcmv and Gbm Associationmentioning

confidence: 99%

The association between human cytomegalovirus and glioblastomas: a review

Hochhalter¹,

Carr²,

O’Neill³

et al. 2017

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Human cytomegalovirus (HCMV) was reported in glioblastoma multiforme (GBM) over a decade ago and this finding has the potential to increase our understanding of the disease and it offers an alternative tumor-specific therapeutic target. Due of this promise, there is a fair amount of time, energy and money being directed towards understanding and utilizing this connection for eventual therapeutic purposes. Nevertheless, the association between GBM and HCMV remains controversial. Several studies have reported conflicting results, further undermining the potential clinical value of this association. In this review, the authors will discuss the latest developments on this evolving issue. Specifically, the results of the latest studies, both positive and negative, will be discussed. Furthermore, potential theories to explain discrepancies reported in the literature will be proposed. Clinical implications including potential targets for anti-HCMV therapy and the latest developments in anti-HCMV therapy will be presented. Finally, solutions to remedy this controversial issue in neuro-oncology will be offered. ReviewThis is an open access article distributed under the terms of the Creative Commons AttributionNonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

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Cytomegalovirus as an oncomodulatory agent in the progression of glioma

Cited by 49 publications

References 96 publications

Lack of human cytomegalovirus expression in single cells from glioblastoma tumors and cell lines

Lack of human cytomegalovirus expression in single cells from glioblastoma tumors and cell lines

A Dendritic Cell-Targeted Adenoviral Vector Facilitates Adaptive Immune Response Against Human Glioma Antigen (CMV-IE) and Prolongs Survival in a Human Glioma Tumor Model

The association between human cytomegalovirus and glioblastomas: a review

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