Concise Review: Targeting cancer stem cells and their supporting niche using oncolytic viruses

Cancer stem cells and their surrounding immunosuppressive niche – a welcoming environment for oncolytic viruses. The immunosuppressive tumor microenvironment results from recruitment of regulatory T cells (Tregs), tumor ‐associated macrophages (TAMs), myeloid‐derived suppressor cells (MDSCs) and tumor‐associated neutrophils (N2), as well as hypoxic conditions which downregulate MHC and decrease recruitment of T cells. Other immune cells, such as natural killer (NK) and dendritic cells (DC), may also have diff iculty penetrating the stiff extracellular matrix. Oncolytic viruses are endowed with an inherent oncotropism, and have the potential to spark an immunological “fire” in the tumor microenvironment. AbstractCancer stem cells (CSCs) have the capacity to self ‐renew and differentiate to give rise to heterogenous cancer cell lineages in solid tumors. These CSC populations are associated with metastasis, tumor relapse and resistance to conventional anti‐cancer therapies. Here, we focus on the use of oncolytic viruses (OVs) to target CSCs as well as the OV‐driven interferon production in the tumor microenvironment (TME) that can repress CSC properties. We explore the ability of OVs to deliver combinations of immune‐modulating therapeutic transgenes, such as immune checkpoint inhibitor antibodies. In particular, we highlight the advantages of v irally‐encoded bi‐specific T cell engagers (BiTEs) to not only target cell‐surface markers on CSCs, but also ...
Source: Stem Cells - Category: Stem Cells Authors: Tags: Cancer Stem Cells Source Type: research