1. Nat. Rev. Urol. doi:10.1038/nrurol.2018.10
Figure 2 Subversion of prostate-cancer-associated immunosuppression by oncolytic viruses
Figure 2 | Subversion of prostate-cancer-associated immunosuppression by oncolytic viruses. The prostate cancer microenvironment hosts multiple immunosuppressive strategies that restrict the development of antitumour immune responses. Lymphocytes, such as natural killer (NK) cells and CD4+ and CD8+ T cells remain in an anergic state and can express inhibitory immune checkpoint receptors, such as programmed cell death protein 1 (PD1) and cytotoxic T lymphocyte antigen 4 (CTLA4). Antigen-presenting cells (APCs), including macrophages (MΦ) and dendritic cells (DCs), have reduced or no expression of major histocompatibility complex (MHC) molecules and co-stimulatory molecules, as well as reduced antigen processing and presentation capacities. In addition, the tumour expresses inhibitory immune checkpoint receptors, such as programmed cell death 1 ligand 1 (PDL1) and V-type immunoglobulin domain-containing suppressor of T cell activation (VISTA), and harbours immunosuppressive cells (such as regulatory T (Treg) cells and myeloid-derived suppressor cells (MDSCs)), cytokines (such as transforming growth factor-β (TGFβ) and IL-10), and metabolic products (such as, indoleamine 2,3-dioxygenase (IDO) and prostaglandin E2 (PGE2)). Collectively, this microenvironment-associated immunosuppression inhibits the antitumour action of immune cells. Following administration, oncolytic viruses trigger an antiviral immune response that includes the release of type I interferons and other pro-inflammatory cytokines. This antiviral response overcomes the effects of the suppressive milieu and drives the recruitment of immune cells to the tumour microenvironment. Oncolytic viruses also act on NK cells and APCs and reinstate their cytolytic and antigen-presenting capacities, respectively. In addition, oncolytic killing of cancer cells releases otherwise unavailable tumour antigens, which are then processed and presented by APCs. These tumour-antigen-displaying, mature APCs stimulate tumour-specific T cell immunity. Thus, oncolytic-virus-driven immunological events can subvert the immunosuppression that is associated with the tumour microenvironment and initiate antitumour immunity.
Lee, P. & Gujar, S. (2018) Potentiating prostate cancer immunotherapy with oncolytic viruses
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