In the field of immunotherapy, oncolytic viruses (OVs) hold a special place at the crossroad of various antitumor mechanisms. Due to their ability to specifically target and kill cancer cells without replicating in the healthy ones, they have been extensively studied over the last two decades for their direct cytotoxic properties; tens of RNA or DNA viruses exhibiting natural or engineered oncolytic properties have been demonstrated to exert antitumor effects, in vitro, in vivo and in patients, against a wide variety of human malignancies, including aggressive cancers such as multiple myeloma, metastatic melanoma or hepatocellular carcinoma 
While focusing on induction of cancer cell death and tumor regressions related to viral replication, the field as a whole sometimes overlooked the role of the immunotherapeutic effects in the extremely promising results obtained with OVs at the bench or in patients. When considering data that have been accumulating over the years on OVs, results related to the basic immunological mechanisms at play are fragmented, and comprehensive understanding of how exactly the immune system participates to the therapeutic activity of these agents in patients is rather incomplete.
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