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.
Highlights
Glioblastoma multiforme (GBM) is intractable and among the most lethal human cancers
GBM has a median survival of 14 months, and its 5-year survival rate has remained unchanged for nearly half a century, even in the face of new standards of care [4,5,6]
Studies linking human endogenous retroviruses (HERVs) to GBM are sparse, but there appears to be active interest in determining if HERVs contribute to human cancers
Summary
Glioblastoma multiforme (GBM) is intractable and among the most lethal human cancers. Many theories have been advanced for why GBM is universally lethal and intransigent. It harbors a bland mutagenomic profile relative to other cancers, due in part to a few canonical mutations driving oncogenesis as opposed to carcinogens [7]. The New Yorker to say, “If I ever get a GBM, put your finger in your keister and put it in the wound” [14] This sounds less elegant than checkpoint blockade, but for reasons that will be advanced in this review, such an approach (or an adjacent—more regulated—approach in the vein of deliberate viral infection) is likely to bear more fruit than typical immunotherapeutic strategies
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
