**19. Integrating immunotherapy with oncolytic viruses for cancer treatment**

The antitumor activity of oncolytic viruses involves multiple mechanisms that encompass the natural interactions between viruses, tumor cells and the immune system [140]. During the last decade oncolytic viruses are becoming an effective means in cancer treatment. Viruses have developed sophisticated means to escape immune surveillance and which can be manipulated for therapeutic purposes to stimulate anti-cancer immune response. Likewise, nearby infusion of oncolytic virus into a tumor site can incite an abscopal impact, in which distant, uninfected tumors additionally go through insusceptible immune rejection [141]. This abscopal effect is caused by oncolytic viruses' sequential activity, multiply in cancer cells and then progresses to activation of immunogenic cell death, which results in the release of antigens and danger factors, which then enhance both innate and adaptive antitumor immune responses. Furthermore, oncolytic viruses can be genetically modified to express therapeutic genes, which can improve antitumor activity even more. In the absence of viral replication, viral encoded gene expression allows immune regulation against tumors while restricting the antiviral immune response [142]. This points out, oncolytic viruses are highly adaptable agents that offer a critical 'on' switch that enhances the migration of tumor infiltrating lymphocytes into the tumor stroma, and this can be exploited to improve antigen-specific immune responses as part of combo-immuno therapies.
