**2. Oncolytic Virus Effects on TME**

The long-term effects of immunotherapy in solid tumors are mostly unsatisfactory, partly due to the immunosuppressive condition of TME and low infiltration of immune cells. TME consists of tumor cells, tumor-associated fibroblasts (TAF), vEC, mesenchymal cells, myeloid-derived suppressor cells (MDSCs), and tumor-infiltrating leukocytes (TILs), such as T cells, B cells, dendritic cells (DCs), natural killer (NK) cells, macrophages, and neutrophils [90]. The presence of exhausted cytotoxic T lymphocytes (CTLs), helper T-cells (THs), and NK cells, as well as a large number of regulatory T-cells (Tregs), tolerogenic DCs, MDSC, and M2-macrophages, induce immunosuppressive milieu in the TME through inhibitory ligands and secretion of inhibitory cytokines such as interleukin (IL)-10, tumor growth factor (TGF)-β, IL-35, and IL-27 [91]. OVs can change the paradigm in the TME and convert cold tumors to hot ones by various mechanisms.
