Fig. 6: Proposed mechanisms of tumor clearance in facilitated by a multidose OVT protocol. | Communications Biology

Fig. 6: Proposed mechanisms of tumor clearance in facilitated by a multidose OVT protocol.

From: Repeated dosing improves oncolytic rhabdovirus therapy in mice via interactions with intravascular monocytes

Fig. 6

Following the first dose of OV, virus is observed binding to the endothelium and neutrophils intravascularly, and tumor cells within the tissue initiating tumor cell infection. Once foci of infection have been generated recruitment of neutrophils to the foci is observed. Over the course of the next 24 h the neutrophils limit the tumor cell infection. Monocytes become abundant in the tumor vasculature and following a second dose of VSV are frequently observed capturing virus particles. This second dose of virus leads to enhanced infection from the first dose of virus by modulating the tumor environment in a monocyte-dependent fashion. Virus bound monocytes interact with neutrophils within the vessels, the cytokine profile within the tumor is altered, neutrophil recruitment is reduced, and CD8 + T cell numbers increased. Oncolysis of the tumor cells from the enhanced first dose, in addition to increased numbers of CD8 + T cells 24 h following the second dose synergize to result in more effective tumor clearance compared to a single dose of OV.

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