Remodeling the tumor microenvironment by oncolytic viruses: beyond oncolysis of tumor cells for cancer treatment

Abstract

Tumor cells manipulate the local environment in which they grow, creating a tumor microenvironment (TME) that promotes tumor survival and metastasis. The TME is an extremely complex environment rich in immunosuppressive cells and cytokines. Various methods to therapeutically target the complicated TME are emerging as a potential approach for cancer treatment. Oncolytic viruses (OVs) are one of the most promising methods for remodeling the TME into an antitumor environment and can be used alone or in combination with other immunotherapy options. OVs replicate specifically in tumor cells and can be genetically engineered to target multiple elements of the TME simultaneously, thus representing a therapeutic with the potential to modify the TME to promote activation of antitumor immune cells and overcome tumor therapeutic resistance and recurrence. In this review, we analyze the tropism of OVs towards tumor cells and explore the interaction between OVs and immune cells, tumor stroma, vasculature and the metabolic environment in detail to help understand how OVs may be one of our most promising prospects for long-term curative therapies. We also discuss some of the challenges associated with TME therapies, and future perspectives in this evolving field.

Efficacy and safety of oncolytic virus combined with chemotherapy or immune checkpoint inhibitors in solid tumor patients: A meta-analysis

“…Lysing the host cells through self-replication forms a direct effect of OVs ( Achard et al, 2018 ). Destroying the tumor microenvironment (TME) and inducing anti-tumor response are the major mechanisms of OVs ( Bai et al, 2019 ; Wang et al, 2022 ). With these mechanisms, OVs lends a support for ICIs therapy by upregulating PD-L1 of tumor cells ( Zhou et al, 2022 ).…”

Compartmentalization of the host microbiome: how tumor microbiota shapes checkpoint immunotherapy outcome and offers therapeutic prospects

“… 112 Irrespective, particular bacterial species, genera, families, etc and/or the totality of the tumor-associated microbiome may modulate the behavior of established tumors and influence both natural and treatment-reinforced anticancer immunity. Finally, it is also important to note that some bacteria (eg, Bifidobacterium ) 80 113 and oncolytic viruses (eg, vesicular stomatitis virus) 114 have a natural tropism to colonize/infect tumors after systemic administration.…”

Oncolytic Viruses for the Treatment of Bladder Cancer: Advances, Challenges, and Prospects

“…Interferons’ counterregulatory effects can also increase the production of immunological checkpoint molecules by tumor cells, such as galectin 9 and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), as well as programmed cell death 1 ligand 1 (PD-L1) [ 24 ]. The immune suppressive TME is finally broken down by OVs to produce an immunologically “hot” TME that promotes the eradication of primary, metastatic, or recurrent tumor cells [ 25 , 26 , 27 ].…”