Fig. 1

Activating the immune system for cancer rejection with oncolytic virus therapy. The tumor microenvironment of advanced cancers is “cold” due to the lack of immunological activity. Oncoytic virus therapy restores the immunological activity of immune tumor infiltrates. a Danger signal release and DC maturation. Oncolytic adenoviruses infect tumor cells and cause oncolysis, releasing new virus progeny but also DAMPS and PAMPS, which will activate nearby dendritic cells and foster their maturation by upregulating co-stimulatory markers, such as CD80, CD83, and CD86. b Mature dendritic cells will process tumor debris and present tumor-associated and virus antigens to local and distant T cells. Concurrently, the ongoing virus infection attracts T cells to the tumor site. c The activation of B cells by CD4+ T cells or BCR-virus interaction causes the release of neutralizing antibodies, which mark infected tumor cells for ADCC by NK cells, or phagocytosis by M1 macrophages. d CD8+ T cells and NK cells destroy infected and non-infected tumor cells through INFg/GranzB and GranzB/Perforins, respectively. The oncolytic adenovirus infection also upregulates class I HLA in tumor cells, allowing for increased exposure to CD8+ T cells. Overall, the components of this modulation allow the tumor microenvironment to become “hot” with increased immunological activity. DAMP danger-associated molecular patterns, PAMP pathogen-associated molecular patterns, HLA human leukocyte antigen, BCR B cell receptor