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Although originally prized for their direct tumor cytotoxicity (<jats:italic>oncolytic virotherapy<\/jats:italic>), recently, the proinflammatory and immunogenic effects of viral tumor infection (<jats:italic>oncolytic immunotherapy<\/jats:italic>) have come into focus. Indeed, a capacity for eliciting broad, sustained antineoplastic effects stemming from combined direct viral cytotoxicity, innate antiviral activation, stromal proinflammatory stimulation, and recruitment of adaptive immune effector responses is the greatest asset of oncolytic viruses. However, it also is the source for enormous mechanistic complexity that must be considered for successful clinical translation. Because of fundamentally different relationships with their hosts (malignant or not), diverse replication strategies, and distinct modes of tumor cytotoxicity\/killing, oncolytic viruses should not be referred to collectively. These agents must be evaluated based on their individual merits. In this review, the authors highlight key mechanistic principles of cancer treatment with the polio:rhinovirus chimera PVSRIPO and their implications for oncolytic immunotherapy in the clinic. <jats:bold><jats:italic>Cancer<\/jats:italic> 2014;120:3277\u20133286.<\/jats:bold> \u00a9 <jats:italic>2014 American Cancer Society<\/jats:italic>.<\/jats:p>","DOI":"10.1002\/cncr.28862","type":"journal-article","created":{"date-parts":[[2014,6,17]],"date-time":"2014-06-17T13:25:06Z","timestamp":1403011506000},"page":"3277-3286","source":"Crossref","is-referenced-by-count":70,"title":["Oncolytic polio virotherapy of cancer"],"prefix":"10.1002","volume":"120","author":[{"given":"Michael C.","family":"Brown","sequence":"first","affiliation":[{"name":"Department of Surgery Duke Cancer Institute, Duke University Medical Center Durham North Carolina"},{"name":"Division of Neurosurgery Duke Cancer Institute, Duke University Medical Center Durham North Carolina"},{"name":"Department of Molecular 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