The association between human cytomegalovirus and glioblastomas: a review

Abstract

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.

Human Endogenous Retroviruses in Glioblastoma Multiforme

“…Risk factors for GBM include exposure to ionizing radiation [ 5 ], certain use of electronics [ 6 , 7 , 8 ], and infection by viruses such as human cytomegalovirus (HCMV) [ 9 , 10 , 11 ]. The biological mechanism of GBM remains a topic of controversy [ 12 , 13 ]. Therapy for GBM remains challenging due to the lack of efficient biomarkers and drug targets [ 14 ].…”

Immune Landscape of CMV Infection in Cancer Patients: From “Canonical” Diseases Toward Virus-Elicited Oncomodulation

“…Some studies put extra emphasis on the indirect role of CMV in cancer (115,116). For instance, Dey et al suggested that the association between glioma and CMV is an "observational association" (117).…”

“…Some studies put extra emphasis on the indirect role of CMV in cancer ( 115 , 116 ). For instance, Dey et al.…”

“…Despite its viral replication suppression, valganciclovir doesn’t eradicate the virus. Thus, short-term valganciclovir treatment wouldn’t be ideal for treating glioma patients, necessitating long-term treatment to maintain the tumor suppressive properties ( 116 ). Interestingly, valganciclovir treatment outcome was improved in combination with celecoxib (COX-2 specific inhibitor).…”

“…The fact that a high percentage of GMB samples were HCMV-positive has led to potential immunotherapy targets for GBM treatment. HCMV-specific proteins (IE1, pp65, and gB) are being investigated for the development of immunotherapy targets ( 116 , 174 ). Interestingly, a study showed that CMV-stimulated NK cells and γδ-T-cells might have antineoplastic potential and CMV reactivation has been associated with minimal risk for relapsed leukemia in hematopoietic stem-cell transplantation (HSCT) patients ( 173 ).…”