Glioblastoma microenvironment and its reprogramming by oncolytic virotherapy

Abstract

Glioblastoma (GBM), a highly aggressive form of brain tumor, responds poorly to current conventional therapies, including surgery, radiation therapy, and systemic chemotherapy. The reason is that the delicate location of the primary tumor and the existence of the blood-brain barrier limit the effectiveness of traditional local and systemic therapies. The immunosuppressive status and multiple carcinogenic pathways in the complex GBM microenvironment also pose challenges for immunotherapy and single-targeted therapy. With an improving understanding of the GBM microenvironment, it has become possible to consider the immunosuppressive and highly angiogenic GBM microenvironment as an excellent opportunity to improve the existing therapeutic efficacy. Oncolytic virus therapy can exert antitumor effects on various components of the GBM microenvironment. In this review, we have focused on the current status of oncolytic virus therapy for GBM and the related literature on antitumor mechanisms. Moreover, the limitations of oncolytic virus therapy as a monotherapy and future directions that may enhance the field have also been discussed.

Glioblastoma Therapy: Past, Present and Future

“…Genetic modification can have other purposes, such as to enhance the safety of OVs, to improve the tropism of OVs to cancer cells, and to enhance the anti-tumor effect of OVs [ 843 ]. For instance, the genetically attenuated and modified ZIKV strain selectively targets GSCs and exhibits good oncolytic activity [ 844 ].…”

“…In addition, OVs have many advantages over conventional immunotherapies, including precise targeting, effective killing rates, and minimal adverse reactions [ 858 ]. To date, several clinical trials have been carried out for oncolytic viruses to improve the treatment of GB [ 836 , 843 , 857 ]. Examples include adenovirus [ 859 , 860 , 861 ], herpes simplex virus [ 862 , 863 , 864 ], reovirus [ 865 , 866 ], parvovirus [ 867 ], measles virus [ 868 , 869 , 870 ], poliovirus [ 853 , 871 ], vaccinia virus [ 872 ] and Newcastle disease virus [ 873 ].…”

Novel Therapies in Glioblastoma Treatment: Review of Glioblastoma; Current Treatment Options; and Novel Oncolytic Viral Therapies

“…Inducing an immunological response to inadvertently kill cancer cells through several mechanisms, including apoptosis, necrosis, and autophagy, is known as immunogenic cell death (ICD) [ 73 , 74 , 75 ]. Releases of damage-associated molecular patterns (DAMPs), viral pathogen-associated molecular patterns (PAMPs), tumor-associated antigens (TAAs), and several other cytokines are indicative of this [ 76 , 77 ]. Oncolytic viruses enhance the function of antigen-presenting cells (APCs), which reach lymph nodes to recruit cytotoxic CD8+ T lymphocytes (CTLs) and attract them to the infection site, where they destroy tumor-inducing cells [ 78 , 79 , 80 ].…”

Immunotherapy: a promising approach for glioma treatment

“…OV therapy hasadvantage in this era of mature genetic engineering. There are three purposes for genetic modification of OVs: 1) delete virulence genes to improve the safety of OVs, 2) enhance the tumor cell tropism and targeting of OVs to tumor cells, and 3) modify OVs with different therapeutic genes to enhance anti-tumor effects ( 64 ). On the one hand, OVs can self-replicate in host cancer cells, leading to direct lysis of the cancer cells ( 63 ).…”