Abstract
Oncolytic viruses infect, replicate in, and kill cancer cells, leaving normal cells unharmed; they also recruit and activate immune cells against tumor cells. While clinical indications for viroimmunotherapy are growing, barriers to widespread treatment remain. Ensuring real-time tracking of viral replication and resulting anti-tumor immune responses will overcome some of these barriers and is thus a top priority. Clinically optimizing trackability of viral replication will promote safe dose increases, guide serial dosing, and enhance treatment effects. However, viral delivery is only half the story. Oncolytic viruses are known to upregulate immune checkpoint expression, thereby priming otherwise immunodeficient tumor immune microenvironments for treatment with checkpoint inhibitors. Novel modalities to track virus-induced changes in tumor microenvironments include non-invasive measurements of immune cell populations and responses to viroimmunotherapy such as (1) in situ use of radiotracers to track checkpoint protein expression or immune cell traffic, and (2) ex vivo labeling of immune cells followed by nuclear medicine imaging. Herein, we review clinical progress toward accurate imaging of oncolytic virus replication, and we further review the current status of functional imaging of immune responses to viroimmunotherapy.