Viral Control of Glioblastoma

Abstract

Glioblastoma multiforme (GBM) is a universally lethal cancer of the central nervous system. Patients with GBM have a median survival of 14 months and a 5-year survival of less than 5%, a grim statistic that has remained unchanged over the last 50 years. GBM is intransigent for a variety of reasons. The immune system has a difficult time mounting a response against glioblastomas because they reside in the brain (an immunologically dampened compartment) and generate few neoantigens relative to other cancers. Glioblastomas inhabit the brain like sand in the grass and display a high degree of intra- and inter-tumoral heterogeneity, impeding efforts to therapeutically target a single pathway. Of all potential therapeutic strategies to date, virotherapy offers the greatest chance of counteracting each of the obstacles mounted by GBM. Virotherapy can xenogenize a tumor that is deft at behaving like “self”, triggering adaptive immune recognition in an otherwise immunologically quiet compartment. Viruses can also directly lyse tumor cells, creating damage and further stimulating secondary immune reactions that are detrimental to tumor growth. In this review, we summarize the basic immune mechanisms underpinning GBM immune evasion and the recent successes achieved using virotherapies.

Protein structuromics: A new method for protein structure–function crosstalk in glioma

“…Thus, the complex system and microenvironment dynamically support glioma occurrence and development. Research has always focused on the genome, and transcriptomics, including promoter mutations, 45 viral insertions, 46 chromosome translocation or gene amplification, 47 are the most frequent driver gene alterations. However, genotypes and phenotypes of glioma are associated with the balance between oncogenes and anti-oncogenes.…”

Recognition of Differentially Expressed Molecular Signatures and Pathways Associated with COVID-19 Poor Prognosis in Glioblastoma Patients

“…Glioblastoma can have a substantial impact on patients’ brain and immune systems. As a result, any additional disease in these people can reduce their chances of survival [ 1 , 2 ]. Therefore, there is a need to protect the glioblastoma patient from other diseases.…”

“…Therefore, there is a need to protect the glioblastoma patient from other diseases. A recent study suggested that the boost in GBM due to viral infection and its high mortality rate might because of a lack of specific treatment [ 2 ]. The survival status of patients during the viral–glioblastoma association has already been proven by using in vitro xenograft models [ 3 ].…”

The Basis and Advances in Clinical Application of Cytomegalovirus-Specific Cytotoxic T Cell Immunotherapy for Glioblastoma Multiforme

“…There is a plethora of evidence that human cytomegalovirus (HCMV) antigens are abundantly expressed in GB tissue but not in normal brain tissue and potentially contribute to gliomagenesis ( 10 ). However, since the 80-90% prevalence of HCMV in healthy adults does not correspond to the prevalence of GB (1 out of 30,000), HCMV is not labeled as a classic oncogenic virus ( 11 , 12 ). Thereby, HCMV does not directly induce malignant cellular transformation, but rather contributes to GB pathogenesis via “oncomodulation” of host cellular pathways ( 13 ).…”