Oncolytic viruses (OVs) are at the forefront of biologicals for cancer treatment. They represent a diverse landscape of naturally occurring viral strains and genetically modified viruses that, either as single agents or as part of combination therapies, are being evaluated in preclinical and clinical settings. As the field gains momentum, the research on OVs has been shifting efforts to expand our understanding of the complex interplay between the virus, the tumor and the immune system, with the aim of rationally designing more efficient therapeutic interventions. Nowadays, the potential of an OV platform is no longer defined exclusively by the targeted replication and cancer cell killing capacities of the virus, but by its contribution as an immunostimulator, triggering the transformation of the immunosuppressive tumor microenvironment (TME) into a place where innate and adaptive immunity players can efficiently engage and lead the development of tumor-specific long-term memory responses. Here we review the immune mechanisms and host responses induced by ssRNA(-) (negative-sense single-stranded RNA) viruses as OV platforms. We focus on two ssRNA(-) OV candidates: Newcastle disease virus (NDV), an avian paramyxovirus with one of the longest histories of utilization as an OV, and influenza A (IAV) virus, a well-characterized human pathogen with extraordinary immunostimulatory capacities that is steadily advancing as an OV candidate through the development of recombinant IAV attenuated platforms.
Keywords: IAV; ICD; NDV; Oncolytic virus; cancer vaccine; immunotherapy; in situ vaccination; orthomyxovirus; paramyxovirus; ssRNA(−); tumor microenvironment; virotherapy.